ovalbumin and Prediabetic-State

Diabetes is known to be regulated by cytokines secreted from Th1 cells, while allergic rhinitis (AR) is mainly regulated by Th2 cytokines. In recent past we have reported the development of diabetes in response to parthinium induced AR to rats. These results were contradictory to Th1/Th2 paradigm which suggests that Th1 and Th2 cells reciprocally counteract each other. Subsequently in silico interactome analysis further revealed that Th2 cytokines may signal to increase the level of Th1 along with the proteins involved in the development of diabetes. In present study we tried to understand the diabetogenic changes on the background of ovalbumin induced allergic rhinitis (OVA). Three groups of seven rats were considered; group I control (Ctrl); group II OVA and group III OVA+L-cetrizine (OVA+ D). The study continued for 48 days and the experiment was terminated on day 49, while L-cetrizine was administered for last 07 days (42-48 days). Group II showed increased levels of Th1 (IL-2) and Th2 cytokines, induction of allergic rhinitis and changes in the proteins involved in diabetes. In group III, most of the changes were reverted back towards normalcy. Induction of allergic rhinitis triggers Th2 cytokines that result increase IL-2 (Th1) and alterations in the metabolic parameters led to the condition of prediabetes.

Topics: Animals; Cells, Cultured; Cytokines; Humans; Inflammation Mediators; Male; Ovalbumin; Prediabetic State; Rats; Rats, Wistar; Rhinitis, Allergic, Perennial; Th1 Cells; Th1-Th2 Balance; Th2 Cells

Insulin-dependent diabetes mellitus (IDDM) is caused by autoimmune destruction of pancreatic beta cells with the primary mechanism being cell mediated. The BB rat develops insulitis and IDDM with many features analogous to the disease in man. In previous studies we reported that weekly administration of 2'-deoxycoformycin (dCF) for four months reduces significantly the incidence of IDDM in the BB rat by 70%, and that the animals remain free of diabetes for a minimum of two months after drug withdrawal. Since the diabetes-prone BB rat is lymphopenic, with a reduction of both CD4 and CD8 cells, the continuous failure of dCF treated animals to develop diabetes may have been due to generalized immunosuppression. To test this possibility, the ability of dCF treated diabetes-free BB rats to mount an immune response after challenge with Ovalbumin was examined five months after drug withdrawal. The results showed that the post-immunization levels of total IgG and specific IgG in these animals did not differ from those observed in non-dCF treated controls nor those of control diabetes-resistant non-lymphopenic BB rats. Moreover, FACS analysis indicated no change in the percentages of total numbers of CD4+ or CD8+ cells between the two groups of animals. Histological assessment of the pancreata of the post-dCF treated animals showed varying degrees of mononuclear cell infiltrates in the islets. These data demonstrate that treatment by dCF is not permanent, and may require intermittent or continuous administration to prevent development of diabetes. Further studies are needed to determine the mechanism of action of dCF in this model of IDDM.

Topics: Animals; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Diabetes Mellitus, Type 1; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; Humans; Immunoglobulin G; Immunosuppressive Agents; Immunotherapy; Islets of Langerhans; Ovalbumin; Pentostatin; Prediabetic State; Rats; Rats, Inbred BB