DBA/1 mice were administered
type II collagen (CII) or
collagen peptides intranasally before systemic immunization to determine whether tolerance could be induced and autoimmune
arthritis suppressed. Although prior experiments have demonstrated that
collagen given intravenously or orally is effective, the respiratory mucosal route offers several theoretical 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-2q mice were all effective in reducing the incidence and severity of
arthritis and the immune response to CII. Since previous studies have demonstrated the importance of
IgG2 antibody subclasses to the induction of
collagen-induced arthritis, total
immunoglobulin G (
IgG),
IgG1, and
IgG2a and
IgG2b were measured.
IgG2 antibody subclasses were significantly downregulated by the treatment regimen, whereas a slight decrease in
IgG1 antibodies was noted that was not significant. In an effort to determine the mechanism by which
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, whereas a Th1-like response was detected in immunized mice not tolerized with CII. These findings indicate that the downregulation of
arthritis that occurs with
intranasal administration of CII is associated with Th2-type lymphokine profile and a decrease in
complement-fixing antibody subclass.