SUPPRESSION OF MURINE COLLAGEN-INDUCED ARTHRITIS BY NASAL ADMINISTRATION OF COLLAGEN

DBA/1 mice were administered type II collagen (CII) or collagen peptid es intranasally before systemic immunization to determine whether tole rance could be induced and autoimmune arthritis suppressed. Although p rior experiments have demonstrated that collagen given intravenously o r orally is effective, the respiratory mucosal route offers several th eoretical advantages for dosing peptides, in addition to ease of use. Intact CII, CB11 and a synthetic peptide containing the immunodominant T-cell epitope recognized by H-2(q) mice were all effective in reduci ng the incidence and severity of arthritis and the immune response to CII. Since previous studies have demonstrated the importance of IgG2 a ntibody subclasses to the induction of collagen-induced arthritis, tot al immunoglobulin G (IgG), IgG1, and IgG2a and IgG2b were measured. Ig G2 antibody subclasses were significantly downregulated by the treatme nt regimen, whereas a slight decrease in IgG1 antibodies was noted tha t was not significant. In an effort to determine the mechanism by whic h arthritis was attenuated, cervical lymph node and spleen cells from treated mice were cultured separately with CII and supernatants tested for the presence of T-cell lymphokines. The cells provided a T-helper 2 (Th2)-like response to CII, with T cells from lymph nodes secreting interleukin-4 (IL-4) and splenocytes secreting both IL-4 and IL-10, w hereas a Th1-like response was detected in immunized mice not tolerize d with CII. These findings indicate that the downregulation of arthrit is that occurs with intranasal administration of CII is associated wit h Th2-type lymphokine profile and a decrease in complement-fixing anti body subclass.