Cytokines Mediating Inflammation in a Model of Secondary Immunodeficiency in Wistar Rats: Immunomodulation Triggered by Thymomodulin

Abstract

We have previously demonstrated in a rat model of immunodeficiency, an increase in the number of yo T cells in the gut lamina propria and in the number of CD8aa+, CD25+, y8+ subpopulations of intestinal intraepithelial lymphocytes (iIEL). The increased percentage of CD8aa+ iIEL that express CD25 indicates inflammation. The present study confirms the existence of an inflammatory process in the immunodeficient animals (R21) that is not detectable at the histological level but is characterized by an increase ofthe pro-inflammatory cytokines TNF-a and IFN-y. We have shown a direct relationship between TNF receptor II (TNF-RII) expression and the higher levels of the y8+ iIEL expressing TNFa (TCRy8+/TNF-a+ cells) that could be indicating a differential T cell reactivity. The effects of the increased expression of inflammatory cytokines such as TNF-a and INF-yseem to be down regulated by the high levels of antigen specific TGF-~expression, which, we believe, is antigen specific and appears to maintain oral tolerance. Finally, in malnourished animals NF-KB remains principally in the cytosol and is unable to translocate to the nucleus, indicating the existence of alterations in the metabolic pathways leading to nuclear factor KB translocation from the cytoplasm to the nucleus. The therapeutic action of the immunomodulator TmB was demonstrated by its capacity to return all the cytokines studied to control levels. Moreover, its effects allowed the transcription factor NF-KB to translocate to the nucleus from the cytosol.The gastrointestinal tract is the central organ for the uptake of fluids and nutrients, and at the same time it forms the main protective barrier between the sterile environment ofthe body and the outside world. Intestinal mucosal lymphocytes, including lamina propria and intestinal intraepithelial lymphocytes (iIEL) serve a critical role in the mucosal immune system. The intestinal intraepithelial lymphocytes provide a unique intestinal defense mechanism due to their qualitative and quantitative contributions to the biology of the mucosal immune system. The iIEL constitute an unusual immunological compartment and a heterogeneous population of cells (1-2). Thus, intraepitheliallymphocytes are in sentinel locations to potentially serve as regulatory cells for mucosal immune responses. They have a number of important immunological functions, such as cytotoxic activity, secretion of cytokines and modulation of epithelial cell death and regeneration (3). The intestine of higher vertebrates is a major T

Importance of CCL25 in the attraction of T cells and the role of IL-7 on the signaling pathways in intestinal epithelial cells

“…The iIEL gd+T cells population co-express CD8a and CD25 as seen by cytometry (Olmos et al, 2004). Besides, they also co-express the cytokine TNF-a localized in LP and in the IE, (Delettieres et al, 2004;Olmos et al, 2006), accompanied by an increase of the pro-inflammatory cytokine TNF-a in intestinal lavage from animals after re-feeding indicating the presence of an inflammatory process (Olmos et al, 2006). Moreover, the gd T cell population co-express CCL25 differing in percentage distribution in the mucosal villi (Calabrese et al, 2007).…”

Thymomodulin enhances vaccination responses against Streptococcus agalactiae in Nile tilapia

“…Although, some studies have reported that high doses of immunostimulants in combination with vaccines can be immunosuppressive (LOGAMBAL & MICHAEL 2000). Some immunostimulatory peptides have been extracted from the thymus gland and have been used to enhance the resistance to pathogens or tumors and retardation of immune senescence in animal models (RAA 1996, OLMOS et al 2006. Thymomodulin is a calf thymus acid lysate derivative, composed of several peptides with a molecular weight range of 1-10KD, with capacity to modulate bone marrow stem cell proliferation and differentiation (KOUTTAB et al 1989), enhance the phagocytosis in rat macrophages and human polymorphonuclear cells in vitro (BRAGA et al 1993).…”

“…Thymomodulin is a calf thymus acid lysate derivative, composed of several peptides with a molecular weight range of 1-10KD, with capacity to modulate bone marrow stem cell proliferation and differentiation (KOUTTAB et al 1989), enhance the phagocytosis in rat macrophages and human polymorphonuclear cells in vitro (BRAGA et al 1993). Thymomodulin has evidenced therapeutic action to counter the alterations in cytokine expression induced by an immunodeficiency model in rats (OLMOS et al 2006). Nevertheless, up to date, thymomodulin potential as immunostimulant for fish has not been addressed.…”

Involvement of NK Cells against Tumors and Parasites

“…NCC is a chronic inflammation which potentially leads to the development of neoplastic lesions because it results in parasite-modulated host immune responses, release of endogenous carcinogens like nitric oxide in the brain, and DNA damage through genetic intervention. Also, NCC has recently been associated with other local malignant tumors, particularly glioblastoma multiforme, and also some hematological malignancies (94,95).…”