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Complete Adjuvant (complete + adjuvant)
Kinds of Complete Adjuvant Selected AbstractsHeart changes in 17-day-old fetuses of diabetic ICR (Institute of Cancer Research) mothers: Improvement with maternal immune stimulationCONGENITAL ANOMALIES, Issue 1 2009Juan Claudio Gutierrez ABSTRACT Maternal diabetes mellitus is associated with increased fetal teratogenesis, including cardiovascular defects. Non-specific maternal immune stimulation with Freund's complete adjuvant (FCA) or interferon gamma (IFN,) has been associated with protection against birth malformations. Using a diabetic mouse model, late-gestation fetal heart and great vessel morphology were analyzed. Four groups of mice were used: non-diabetic females as a control group, hyperglycemic females induced by streptozotocin as a diabetic group, and diabetic females injected either with FCA or IFN,. At day 17 of gestation, females were euthanized and one fetus was arbitrarily selected per litter for fixation and sectioning. Treatment-induced changes in cardiac development were assessed from digital images of serial sections taken at standardized levels in the thorax. One-way parametric and non-parametric ANOVA and ordinal logistic regression were performed to compare the difference among groups (P < 0.05). Maternal hyperglycemia altered morphology of the late-gestation fetal mouse heart by causing ventricular chamber dilation, sectional myocardial reduction, and an increase in transversal aortic area. FCA protected the fetal heart from cavitary dilation in diabetic mothers. FCA and IFN, protected the fetal heart against reduction of myocardial area, and ascending thoracic aorta dilation. Consequences of late gestation heart chamber dilation and myocardial reduction are not yet known. Maternal immune stimulation partially protected against these developmental defects by mechanisms that remain unclear. [source] Production of a new model of slowly progressive Heymann nephritisINTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 6 2003Arpad Z. Barabas Summary., A slowly progressive autoimmune kidney disease was induced in Sprague Dawley rats by subcutaneous injection of a chemically modified kidney antigen (rKF3), incorporated into Alum and Distemper complex vaccine, followed by subcutaneous injections of an aqueous preparation of the same antigen. Pathogenic autoantibodies developed, which reacted with fixed glomerular nephritogenic antigen. Subsequently, immunopathological events lead to chronic progressive immune complex glomerulonephritis and proteinuria. The slowly developing disease was morphologically and functionally similar to Heymann nephritis (HN). The damage observed in the kidneys of experimental animals at 8 weeks and at the end of the experiment was examined by direct fluorescent antibody test, histology and electron microscopy. The changes were similar to the typical lesions found in HN rat kidneys, but less severe. Animals became proteinuric from 17 weeks onward (instead of the usual 4,8 weeks). By the end of the experiment, at 8 months, 100% of the rats were proteinuric. This new experimental model of autoimmune kidney disease, which is not complicated by intraperitoneal deposition and retention of Freund's complete adjuvant and renal tubular antigens, allowed us to investigate the pathogenesis of the disease processes from a different aspect, and promises to be a useful and improved model for the investigation of future treatment options. [source] Immunization of rainbow trout, Oncorhynchus mykiss (Walbaum), with a low molecular mass fraction isolated from Flavobacterium psychrophilumJOURNAL OF FISH DISEASES, Issue 12 2008E Högfors Abstract Flavobacterium psychrophilum, the causative agent of rainbow trout fry syndrome has become a widespread fish pathogen in freshwater aquaculture worldwide. In this study, a low molecular mass fraction (P25-33), with an approximate weight of 25,33 kDa, was identified among F. psychrophilum strains in an immunoblotting analysis with anti- F. psychrophilum sera. The immunogenic efficacy of the isolated and extracted P25-33 was investigated in two intraperitoneal immunization trials with rainbow trout, Oncorhynchus mykiss (Walbaum). The first trial included immunizations using P25-33 with Freund's complete adjuvant (FCA) and the second trial included immunizations using P25-33, formalin-inactivated whole and sonicated F. psychrophilum cell preparations without FCA. In both trials, antibody titres against F. psychrophilum were analysed with an enzyme-linked immunosorbent assay and the efficacy of the immunizations was determined by a challenge with F. psychrophilum. The P25-33 was shown to give rise to a protective immune response in rainbow trout after immunization with FCA, but not without FCA when a low concentration of P25-33 was used. Instead formalin-inactivated whole and sonicated cells of F. psychrophilum were able to protect the immunized fish more effectively when immunized without FCA. The results suggest that whole or sonicated F. psychrophilum cells could be better candidates for a cost-effective water-based injection vaccine than the immunogenic fraction. [source] Systemic and mucosal antibody response in tilapia, Oreochromis niloticus (L.), following immunization with Flavobacterium columnareJOURNAL OF FISH DISEASES, Issue 10 2004L D Grabowski Abstract Specific antibody responses to Flavobacterium columnare (isolate ATCC 23463T) were characterized in plasma and mucus of tilapia following intraperitoneal (i.p.) injection or immersion immunization with formalin-killed sonicated or whole cell preparations. Fish (30 per treatment) received a primary immunization and were booster immunized 4 weeks later. An enzyme-linked immunosorbent assay was developed for detection and quantification of specific anti- F. columnare antibody, and it was found that formalin-killed sonicated cells in Freund's complete adjuvant (FCA) injected i.p. stimulated a significant systemic antibody response within 2 weeks (mean titre 11 200) which increased to 30 600 following secondary immunization. At 10 weeks post-immunization, the mean titre remained significantly elevated above the controls. Antibodies were also observed in cutaneous mucus of fish immunized i.p. with formalin-killed sonicated cells in FCA at 6 and 8 weeks post-immunization (mean titres 67 and 33, respectively). Although some individual fish responded, mean plasma and cutaneous mucus antibody titres were not significantly greater than controls in any of the other treatment groups. The results of this study demonstrate that tilapia can mount a significant humoral response in plasma and cutaneous mucus to F. columnare, but i.p. immunization with FCA is required to elicit this response. [source] Characterization of serum and mucosal antibody responses and relative per cent survival in rainbow trout, Oncorhynchus mykiss (Walbaum), following immunization and challenge with Flavobacterium psychrophilumJOURNAL OF FISH DISEASES, Issue 12 2002B R LaFrentz Abstract Serum and mucosal antibody responses of juvenile rainbow trout, Oncorhynchus mykiss, were characterized by enzyme-linked immunosorbent assay (ELISA) following immunization with various preparations of formalin-killed Flavobacterium psychrophilum cells. The protective nature of these preparations was then determined by immunizing rainbow trout fry and challenging with the bacterium. Juvenile rainbow trout immunized intraperitoneally (i.p.) with formalin-killed F. psychrophilum emulsified with Freund's complete adjuvant (FCA), and i.p. with formalin-killed F. psychrophilum either with or without culture supernatant generated significant serum antibody responses by 6 and 9 weeks, respectively. Significant mucosal antibody responses were detected by 9 weeks only in fish immunized i.p. with killed F. psychrophilum/FCA. Following immunization and bacterial challenge of rainbow trout fry, protective immunity was conferred in F. psychrophilum/FCA and saline/FCA groups with relative per cent survival values of up to 83 and 51, respectively. Significant protection was not observed in treatment groups immunized by immersion or i.p. without adjuvant at the challenge doses tested. Results suggest that stimulation of non-specific immune factors enhances the ability of fish to mount a protective immune response, but specific antibody appears necessary to provide near complete protection. In this study, an ELISA was developed to monitor anti- F. psychrophilum antibody production in trout. The relationship of such responses to protective immunity suggests that future vaccination strategies against coldwater disease may require stimulation of both the innate and adaptive arms of the immune response. [source] Inflammatory Pain Reduction In Rats By Local Treatment With oATP, A Selective Inhibitor Of P2X7 ATP ReceptorJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 1 2001G Dell'Antonio Peptide neurotransmitters, as substance P or ATP, are released during inflammatiory processes by the nerve endings of sensory fibers. ATP is also released from the cytoplasm of damaged cells at the site of inflammation. It acts at the level of many P2X subtypes of purinoreceptors. The receptor for extracellular ATP named P2Z/P2X7 is selectively blocked by the periodate oxidized ATP (oATP). We have hypothesized that P2X subunits present on peripheral sensory nerve terminals, able to initiate a nociceptive signal, could be blocked by local treatment with oATP, so inducing pain relief. Male inbred Fisher rats weighing about 250 g were used. Unilateral inflammation into rat hind paw was induced by intraplantar injection of Freund's complete adjuvant (FCA). The following signs of inflammation, from 3 to 48 h after FCA injection, were detected: increased paw volume, increased paw temperature and hyperalgesia. The latter was evaluated using an algesiometric test wich measured the paw pressure threshold (PPT, expressed in g). We treated some rats, bearing paw inflammation by 12 h, with local injection of 56 ,M oATP. We showed a significant reduction of hyperalgesia in treated rats (PPT = 190 ± 2.3 in inflamed paw of oATP treated vs. PPT = 60 ± 1.6 in inflamed paw of untreated rats, at 60 min following oATP innoculation). We showed also that treatment with oATP was more efficient than treatment with diclofenac in reducing local inflammatory pain (PPT expressed as percentage of the maximum possible effect = 60 ± 0.5, at 120 min following intraplantar administration of oATP, vs. 25 ± 1.9 at the same time following intraplantar administration of diclofenac). The use of polyclonal antibody anti P2X7 receptor to perform immunohistochemical analysis of inflamed tissue, showed a reduction of receptor expression at the level of nerve endings in sections obtained from rat paw treated with oATP with respect to sections obtained from untreated rats. Such an effect was independent on the recruitment of immunocytes in inflamed tissue. Our results demonstrate that ATP exerts a key role in the pathophysiology of peripheral inflammation and that oATP may be effective in treating inflammatory pain. [source] Knockdown of Fc, receptor III in an arthritic temporomandibular joint reduces the nociceptive response in ratsARTHRITIS & RHEUMATISM, Issue 10 2010Phillip R. Kramer Objective Fc, receptor III (Fc,RIII; CD16) is a receptor expressed on immune cells that selectively binds IgG molecules. IgG binding results in cellular activation and cytokine release. IgG is an important factor in arthritis and can be found in the arthritic temporomandibular joint (TMJ). We undertook this study to test the hypothesis that a reduction in Fc,RIII expression in TMJ tissues would reduce the nociceptive and inflammatory responses in an inflamed joint. Methods Small interfering RNA (siRNA), either naked or complexed with linear polyethyleneimine, was injected into the superior joint space of the TMJ in rats. After administration of siRNA the joint was injected with saline or with Freund's complete adjuvant to induce arthritis. Nociceptive responses were quantitated in the rat by measuring the animal's meal duration. Fc,RIII expression in the TMJ tissue was assayed by immunocytochemistry or Western blotting. Cleavage of Fc,RIII transcript was then assayed by 5, rapid amplification of complementary DNA ends. Interleukin-1, (IL-1,) and IgG content was measured in the TMJ tissue by enzyme-linked immunosorbent assay. Results Injection of Fc,RIII siRNA reduced the amount of Fc,RIII in the TMJ tissues, and the transcript was cleaved in a manner consistent with an RNA interference mechanism. Moreover, injection of Fc,RIII siRNA reduced the nociceptive response of rats with an arthritic TMJ and reduced the amount of the proinflammatory cytokine IL-1,. Conclusion Fc,RIII contributes to the pain resulting from inflammatory arthritis of the TMJ, and siRNA has the potential to be an effective treatment for this disorder. [source] Enhanced Th1 and Th17 responses and arthritis severity in mice with a deficiency of myeloid cell,specific interleukin-1 receptor antagonistARTHRITIS & RHEUMATISM, Issue 2 2010Céline Lamacchia Objective The balance between interleukin-1 (IL-1) and its specific inhibitor, the IL-1 receptor antagonist (IL-1Ra), plays a major role in the development of arthritis. The purpose of this study was to investigate the role of IL-1Ra produced specifically by myeloid cells in the control of collagen-induced arthritis (CIA) by using myeloid cell,specific IL-1Ra,deficient mice (IL-1Ra,M). Methods IL-1Ra,M mice were generated by using the loxP/Cre recombinase system. CIA was induced in IL-1Ra,M mice and littermate control mice by a single immunization with bovine type II collagen (CII) in Freund's complete adjuvant. Arthritis severity was assessed by clinical and histologic scoring. Draining lymph node (DLN) cell responses were examined ex vivo, and ankle extracts were used in the quantification of cytokines and chemokines. Results Clinical and histopathologic evaluations revealed an early disease onset and a severe form of CIA in IL-1Ra,M mice. This was characterized by increased production of interferon-, (IFN,) and IL-17 by CII-stimulated DLN cells. We also observed that the CII-specific CD4+ T cell response shifted in vivo, from a dominant Th1 response early in the course of the arthritis to the presence of both Th1 and Th17 cytokines later in the disease course. Interestingly, IL-1Ra levels were higher in the arthritic joints of IL-1Ra,M mice as compared with the controls, indicating that nonmyeloid cells strongly contribute to the local production of IL-1Ra. However, this enhanced IL-1Ra production was not sufficient to limit joint inflammation and tissue damage. Conclusion Our results suggest that myeloid cell,derived IL-1Ra plays a critical role in the control of the development and the severity of CIA by modulating Th1 and Th17 responses in lymphoid organs. [source] Apolipoprotein E,deficient mice are resistant to the development of collagen-induced arthritisARTHRITIS & RHEUMATISM, Issue 2 2010Darren L. Asquith Objective To determine whether elevated serum lipid levels resulting from feeding animals a high-fat diet can affect the inflammatory process in C57BL/6 (B6) wild-type (WT) and B6 ApoE,/, mouse models of collagen-induced arthritis (CIA). Methods Male B6 WT or ApoE,/, mice were fed either a normal chow diet or a high-fat diet. CIA was induced in mice at 12 weeks of age using type II chicken collagen, Freund's complete adjuvant, and, on occasion, a lipopolysaccharide boost. Expression levels of autoantibodies and cytokines were measured using enzyme-linked immunosorbent assay and multiplex assay, respectively. Results Whereas B6 WT mice developed severe articular inflammation after collagen immunization, ApoE,/, mice developed no clinical or histologic evidence of disease regardless of whether they had been fed a high-fat diet or a normal chow diet. The fact that arthritis was not present in ApoE,/, mice did not result from inadequate production of serum IgG2a collagen antibodies, since levels observed in ApoE,/, mice were similar to those observed in arthritic B6 WT control mice. Critically, development of atherosclerosis in ApoE,/, mice was not affected by the CIA protocol. Conclusion Our findings suggest that ApoE,/, mice are resistant to the development of CIA. Intriguingly, induction of host autoimmunity in the absence of articular inflammation had no effect on atherosclerosis progression, suggesting that articular inflammatory load may be a critical risk factor in vascular pathology. [source] Plasmin immunization preferentially induces potentially prothrombotic IgG anticardiolipin antibodies in MRL/MpJ miceARTHRITIS & RHEUMATISM, Issue 10 2009Kaleo Ede Objective To test the hypothesis, utilizing 2 experimental mouse models, that plasmin is an important autoantigen that drives the production of certain IgG anticardiolipin (aCL) antibodies in patients with the antiphospholipid syndrome. Methods BALB/cJ and MRL/MpJ mice were immunized with Freund's complete adjuvant in the presence or absence of human plasmin. The mouse sera were analyzed for production of IgG antiplasmin, IgG aCL, and IgG anti,,2 -glycoprotein I (anti-,2GPI) antibodies. IgG monoclonal antibodies (mAb) were generated from the plasmin-immunized MRL/MpJ mice with high titers of aCL, and these 10 mAb were studied for their binding properties and functional activity in vitro. Results Plasmin-immunized BALB/cJ mice produced high titers of IgG antiplasmin only, while plasmin-immunized MRL/MpJ mice produced high titers of IgG antiplasmin, IgG aCL, and IgG anti-,2GPI. Both strains of mice immunized with the adjuvant alone did not develop IgG antiplasmin or IgG aCL. All 10 of the IgG mAb bound to human plasmin and cardiolipin, while 4 of 10 bound to ,2GPI, 3 of 10 bound to thrombin, and 4 of 10 bound to the activated coagulation factor X (FXa). Functionally, 4 of the 10 IgG mAb inhibited plasmin activity, 1 of 10 hindered inactivation of thrombin by antithrombin III, and 2 of 10 inhibited inactivation of FXa by antithrombin III. Conclusion Plasmin immunization leads to production of IgG antiplasmin, aCL, and anti-,2GPI in MRL/MpJ mice, but leads to production of only IgG antiplasmin in BALB/cJ mice. IgG mAb generated from plasmin-immunized MRL/MpJ mice bind to various antigens and exhibit procoagulant activity in vitro. These results suggest that plasmin may drive potentially prothrombotic aCL in genetically susceptible individuals. [source] A murine model of mixed connective tissue disease induced with U1 small nuclear RNP autoantigenARTHRITIS & RHEUMATISM, Issue 2 2006Eric L. Greidinger Objective To test whether immunizing mice with autoantigens closely linked to mixed connective tissue disease (MCTD) could induce an MCTD-like clinical syndrome distinguishable from systemic lupus erythematosus (SLE). Methods Transgenic and knockout C57BL/6-derived mice were immunized subcutaneously at age 8,12 weeks with U1,70-kd small nuclear RNP (70K) fusion protein along with either Freund's complete adjuvant (CFA) or U1 RNA. After 2 months, mice were killed and analyzed histologically and serologically. Results Immunization of C57BL/6-derived mice transgenic for human HLA,DR4 with 70K and either CFA or U1 RNA led to anti-70K antibodies in 62% of mice (21 of 34), and diversified anti-RNP immune responses. MCTD-like lung disease also developed in 50% of immunized mice (17 of 34), and anti-70K antibodies were strongly correlated with lung disease. CFA and U1 RNA were comparably able to induce this syndrome. Mice deficient in Toll-like receptor 3 (TLR-3) also developed this same syndrome when immunized with 70K and CFA. However, TLR-3,/, mice failed to develop MCTD-like lung disease when treated with 70K and U1 RNA. Rather, TLR-3,/, mice immunized with 70K and U1 RNA developed an autoimmune syndrome characterized by glomerulonephritis typical of SLE. Conclusion Exposure to 70K in an appropriate context is sufficient to induce autoimmunity and target organ injury consistent with MCTD. This system represents a new model of autoimmune interstitial lung disease, and establishes a closer link between anti-70K immunity and MCTD-like lung disease. Of note, changes in innate immune signaling can cause the same trigger to lead to the development of SLE-like nephritis rather than MCTD-like lung disease. [source] The Critical Role of IL-12p40 in Initiating, Enhancing, and Perpetuating Pathogenic Events in Murine Experimental Autoimmune NeuritisBRAIN PATHOLOGY, Issue 4 2002Lei Bao Interleukin 12 (IL-12) is a proinflammatory cytokine with important immunoregulatory activities and is critical in determining the differentiation and generation of Th1 cells. For the present study, we investigated the role of endogenous IL-12 in the pathogenesis of experimental autoimmune neuritis (EAN), which is a CD4+ T-cell mediated autoimmune inflammatory disease of the peripheral nervous system. EAN is used as an animal model for Guillain-Barré syndrome of humans. Here, EAN was established in IL-12 p40 deficient mutant (IL-12 -/- ) C57BL/6 mice by immunization with P0 peptide 180,199, a purified component of peripheral nerve myelin, and Freund's complete adjuvant. In these IL-12 -/- mice the onset of clinical disease was delayed, and the incidence and severity of EAN were significantly reduced compared to that in wild-type mice. The former group's clinical manifestations were associated with less P0-peptide 180,199 induced secretion of interferon-, (IFN-,) by splenocytes in vitro and low production of anti-P0-peptide 180,199 IgG2b antibodies in serum. Fewer IFN-, and TNF-, producing cells, but more cells secreting IL-4, were found in sciatic nerve sections from IL-12 -/- mice, consistent with impaired Th1 functions and response. However, the IL-12 deficiency appeared not to affect P0 peptide 180,199-specific T-cell proliferation. These results indicate that IL-12 has a major role in the initiation, enhancement and perpetuation of pathogenic events in EAN by promoting a Th1 cell-mediated immune response and suppressing the Th2 response. This information augments consideration of IL-12 as a therapeutic target in Guillain-Barré syndrome and other T-cell-mediated autoimmune diseases. [source] In vivo effects of CB2 receptor-selective cannabinoids on the vasculature of normal and arthritic rat knee jointsBRITISH JOURNAL OF PHARMACOLOGY, Issue 2 2008J J McDougall Background and purpose: Cannabinoids (CBs) are known to be vasoactive and to regulate tissue inflammation. The present study examined the in vivo vasomotor effects of the CB2 receptor agonists JWH015 and JWH133 in rat knee joints. The effect of acute and chronic joint inflammation on CB2 receptor-mediated responses was also tested. Experimental approach: Blood flow was assessed in rat knee joints by laser Doppler imaging both before and following topical administration of CB2 receptor agonists. Vasoactivity was measured in normal, acute kaolin/carrageenan inflamed and Freund's complete adjuvant chronically inflamed knees. Key results: In normal animals, JWH015 and JWH133 caused a concentration-dependent increase in synovial blood flow which in the case of JWH133 was blocked by the selective CB2 receptor antagonist AM630 as well as the transient receptor potential vanilloid-1 (TRPV1) antagonist SB366791. The vasodilator effect of JWH133 was significantly attenuated in both acute and chronically inflamed knees. Given alone, AM630 had no effect on joint blood flow. Conclusion and implications: In normal joints, the cannabinomimetic JWH133 causes hyperaemia via a CB2 and TRPV1 receptor mechanism. During acute and chronic inflammation, however, this vasodilatatory response is significantly attenuated. British Journal of Pharmacology (2008) 153, 358,366; doi:10.1038/sj.bjp.0707565; published online 5 November 2007 [source] Bradyzide, a potent non-peptide B2 bradykinin receptor antagonist with long-lasting oral activity in animal models of inflammatory hyperalgesiaBRITISH JOURNAL OF PHARMACOLOGY, Issue 1 2000Gillian M Burgess Bradyzide is from a novel class of rodent-selective non-peptide B2 bradykinin antagonists (1-(2-Nitrophenyl)thiosemicarbazides). Bradyzide has high affinity for the rodent B2 receptor, displacing [3H]-bradykinin binding in NG108-15 cells and in Cos-7 cells expressing the rat receptor with KI values of 0.51±0.18 nM (n=3) and 0.89±0.27 nM (n=3), respectively. Bradyzide is a competitive antagonist, inhibiting B2 receptor-induced 45Ca efflux from NG108-15 cells with a pKB of 8.0±0.16 (n=5) and a Schild slope of 1.05. In the rat spinal cord and tail preparation, bradyzide inhibits bradykinin-induced ventral root depolarizations (IC50 value; 1.6±0.05 nM (n=3)). Bradyzide is much less potent at the human than at the rodent B2 receptor, displacing [3H]-bradykinin binding in human fibroblasts and in Cos-7 cells expressing the human B2 receptor with KI values of 393±90 nM (n=3) and 772±144 nM (n=3), respectively. Bradyzide inhibits bradykinin-induced [3H]-inositol trisphosphate (IP3) formation with IC50 values of 11.6±1.4 nM (n=3) at the rat and 2.4±0.3 ,M (n=3) at the human receptor. Bradyzide does not interact with a range of other receptors, including human and rat B1 bradykinin receptors. Bradyzide is orally available and blocks bradykinin-induced hypotension and plasma extravasation. Bradyzide shows long-lasting oral activity in rodent models of inflammatory hyperalgesia, reversing Freund's complete adjuvant (FCA)-induced mechanical hyperalgesia in the rat knee joint (ED50, 0.84 ,mol kg,1; duration of action >4 h). It is equipotent with morphine and diclofenac, and 1000 times more potent than paracetamol, its maximal effect exceeding that of the non-steroidal anti-inflammatory drugs (NSAIDs). Bradyzide does not exhibit tolerance when administered over 6 days. In summary, bradyzide is a potent, orally active, antagonist of the B2 bradykinin receptor, with selectivity for the rodent over the human receptor. British Journal of Pharmacology (2000) 129, 77,86; doi:10.1038/sj.bjp.0703012 [source] | ||||||||||