Immunological Events (immunological + event)

Distribution by Scientific Domains

Selected Abstracts

Predominant T helper type 2-inflammatory responses promote murine colon cancers

Emi Osawa
Abstract Colon cancer is one of the most serious complications of inflammatory bowel diseases, especially ulcerative colitis (UC). Previous studies have shown that characteristic immunological event during inflammation in UC is the expression of T helper-type 2 (Th2) cell-derived cytokines. In this study, we investigated the influence of a predominant Th2-type cytokine response in colitis on carcinogen-induced colon tumors. Wild type (WT), interferon gamma (IFN-,) gene deficient (,/,) [Th2 dominant] or interleukin (IL)-4,/, [Th1-dominant] mice of BALB/c background were used in this study. To compare tumor formation, mice were given the carcinogen azoxymethane (AOM) and intrarectal administration of trinitrobenzene sulfonic acid (TNBS), to induce colitis. Thirty-three weeks after initial treatment, the total colon was examined. When IFN-,,/, mice were treated with AOM and TNBS, significantly higher number of tumors were seen (8.4 ± 1.7) than in WT (3.3 ± 2.9) or IL-4,/, (3.1 ± 3.4) mice, which received identical treatments. A separate set of experiment, using less doses of AOM and TNBS also showed the higher frequency of tumor formation in IFN-,,/, mice than in IL-4,/, mice. Histologically, the tumors were well- or moderately-differentiated adenocarcinomas. No invasion into the submucosal or serosal layers of the intestine was seen. In immunohistological staining, some tumors in IFN-,,/, mice showed distinct nuclear expression of ,-catenin, in contrast to the strong membrane staining seen in tumors of IL-4,/, mice. In conclusion, colonic inflammation associated with Th2-donimant cytokine responses enhanced the formation of malignant neoplasms. © 2005 Wiley-Liss, Inc. [source]

Increased expression of mRNA encoding interleukin (IL)-4 and its splice variant IL-4,2 in cells from contacts of Mycobacterium tuberculosis, in the absence of in vitro stimulation

IMMUNOLOGY, Issue 4 2004
Helen A. Fletcher
Summary Expression of interleukin (IL)-4 is increased in tuberculosis and thought to be detrimental. We show here that in healthy contacts there is increased expression of its naturally occurring antagonist, IL-4delta2 (IL-4,2). We identified contacts by showing that their peripheral blood mononuclear cells (PBMC) released interferon (IFN)-, in response to the Mycobacterium tuberculosis -specific antigen 6 kDa early secretory antigenic target (ESAT-6). Fresh unstimulated PBMC from these contacts contained higher levels of mRNA encoding IL-4,2 (P=0·002) than did cells from ESAT-6 negative donors (noncontacts). These data indicate that contact with M. tuberculosis induces unusual, previously unrecognized, immunological events. We tentatively hypothesize that progression to active disease might depend upon the underlying ratio of IL-4 to IL-4,2. [source]

Early responses associated with chronic pathology in murine schistosomiasis

SUMMARY Inbred male CBA/J mice infected with Schistosoma mansoni develop either hypersplenomegaly syndrome (HSS) or moderate splenomegaly syndrome (MSS) by 20 weeks of infection. Pathologically and immunologically, MSS and HSS closely parallel the intestinal and hepatosplenic clinical forms of schistosomiasis in humans, respectively. By 6 weeks after infection, mice that eventually will become MSS develop T cell-stimulatory, cross-reactive idiotypes (CRI) while HSS mice never produce CRI. Because presence of CRI is useful to predict degree of chronic pathology, we used this measure to investigate what other early immunological events occurred in animals destined to develop severe morbidity. At 8 weeks of infection, there was a strong inverse correlation between CRI and splenomegaly, egg counts, and liver hydroxyproline. Similarly, phorbol myristate acetate (PMA)- and ionomycin-stimulated intracellular cytokine expression of IL-4, IL-5, and GM-CSF in splenic CD4+ T cells was inversely correlated with serum CRI and directly correlated with spleen size. In contrast, spleen cell intracellular TNF-, and peritoneal cell production of nitric oxide demonstrated positive correlations with CRI and inverse correlations with measures of morbidity. Surprisingly, IL-10 and IFN-, were not correlated with CRI levels. These studies link chronic pathology to certain immunological responses during the acute phase of schistosomiasis. [source]

Mixed inflammatory/regulatory cytokine profile marked by simultaneous raise of interferon-, and interleukin-10 and low frequency of tumour necrosis factor-,+ monocytes are hallmarks of active human visceral Leishmaniasis due to Leishmania chagasi infection

V. Peruhype-Magalhães
Summary Considering the complexity of the immunological events triggered during active visceral Leishmaniasis (VL), the relevance of the segregation of the immune response during human VL into type 1 and type 2 still remains unclear. For this purpose, in individuals living in risk areas for VL, we have evaluated especially asymptomatic individuals and patients with active VL, the plasmatic levels of cytokines and reactive nitrogen species under ex vivo conditions. In addition, we have also performed an analysis of intracellular cytokine patterns of circulating leucocytes after short-term culture, particularly in the absence of antigenic-specific stimulation, in order to reflect dynamic events of immune response in vivo during Leishmania chagasi infection. Although asymptomatic individuals and non-infected subjects presented a similar immunological profile, an outstanding inflammatory/regulatory profile, based on higher plasmatic levels of cytokines such as interleukin (IL)-8, interferon (IFN)-,, tumour necrosis factor (TNF)-,, IL-6 and IL-10, was associated with clinical status observed in active VL. In this context, we hypothesize that IL-10, through its ability to inhibit anti-leishmanial macrophage activation, associated with the lower frequency of TNF-,+ monocytes and ordinary levels of nitrite and nitrate are the major mechanisms associated with disease onset. [source]