Combined IMIG and immune Ig attenuates inflammatory colitis in mice

Abstract

BackgroundUsing a combination of homologous and heterologous (mouse/human) polyclonal anti-idiotypic Igs and immune Igs in BALB/c mice we have previously reported attenuation of allergic type responses following OVA immunization. We have now investigated attenuation of an inflammatory colitis in C57BL/6 mice receiving dextran sodium sulfate (DSS) in their drinking water, using additional treatment of DSS-exposed mice with combined human Igs, commercial IVIG (given IM, hence hereafter IMIG) as a source of pooled anti-idiotype Ig, and human anti-Tet as immune Ig. MethodsAcute or chronic colitis was induced by DSS in groups of C57BL/6 mice. Mice also received weekly immunotherapy with im injections of polyclonal immune Ig, polyclonal anti-idiotype Ig, or the combined Igs, for a total of 5 injections, beginning with DSS treatment or after 2 cycles of DSS. Weight loss and mortality were monitored daily, and the extent of colitis was determined further using colonic length measurement, and by ELISA measurement of inflammatory cytokines in supernatants from colonic explant cultures. ResultsMice developed colitis in both the acute and chronic models with loss of body weight, shortened colon lengths, and increased expression of inflammatory cytokines in colonic tissue. Loss of body weight, and inflammatory cytokine production, was attenuated only in chronic colitis, and only after combined IMIG and immune Ig treatment, and not in groups receiving only IMIG or immune Ig alone. ConclusionHeterologous combinations of polyclonal IMIG and immune Ig can attenuate inflammatory colitis in mice. Given the described efficacy of this treatment for allergic desensitization, we hypothesize this methodology may have widespread clinic utility.