IMMUNE-SYSTEM ACTIVATION IN C3H HEJBIR MICE EXHIBITING SPONTANEOUS PERIANAL ULCERATION/

We report our initial characterization of the immune system in C3H/HeJ Bir mice that spontaneously develop perianal ulceration. Analysis of l ymphokine production by mucosal and systemic lymphoid cells obtained f rom these mice revealed higher levels of interleukin (IL)-4 in superna tants of in vitro stimulated Peyer's patch and mesenteric lymph node c ells from C3H/HeJBir mice with severe perianal lesions than from C3H/H eJBir mice with mild perianal lesions or from normal C3H/HeJ mice. Sup ernatants that contain the highest amounts of IL-4 contain the lowest amounts of interferon (IFN)-gamma. Peyer's patches and mesenteric lymp h nodes of C3H/HeJBir mice with severe perianal lesions contain approx imately fourfold fewer cells; however, inguinal lymph nodes contain up to 25-fold more cells compared with C3H/HeJ mice. These inguinal lymp h node cells secrete IL-6, and T cells that produce IL-2 or IFN-gamma can be demonstrated. Serum IgE, IgG1, and IgG2a are all increased in C 3H/HeJBir mice with severe perianal ulceration. These results show tha t C3H/HeJBir mice with grossly evident inflammation have activated lym phocytes in both mucosal and systemic lymphoid organs. Understanding m echanisms of lymphocyte activation and regulation in these mice may pr ovide insights into the pathogenesis of perianal ulceration that is of ten associated with Crohn's disease.