Mycoplasma arthritidis mitogen (MAM) is a potent
superantigen secreted by M. arthritidis, an agent of murine
arthritis. Here we compare the abilities of MAM to induce a panel of
cytokines in vitro and in vivo in BALB/c and C3H/HeJ mouse strains that differ in susceptibility to mycoplasmal
arthritis. Splenocytes from both mouse strains produced high levels of all
cytokines by 24 h following in vitro exposure to MAM. No differences in
cytokine profiles were seen irrespective of the MAM dose. However, there were striking differences in
cytokine profiles present in supernatants of splenocytes that had been collected from mice after intravenous (i.v. ) injection of MAM and subsequently rechallenged with MAM in vitro. Splenocytes collected 24 and 72 h after i.v. injection of MAM and challenged in vitro with MAM showed the most marked divergence in the secreted
cytokines. Type 1
cytokines were markedly elevated in C3H/HeJ cell supernatants, whereas they were depressed or remained low in BALB/c cell supernatants. In contrast, the levels of type 2
cytokines were all greatly increased in BALB/c cell cultures but were decreased or remained low in C3H/HeJ supernatants.
Interleukin-12 mRNA and
protein was also markedly elevated in C3H/HeJ mice, as were the levels of
immunoglobulin G2a. The data indicate a major skewing in
cytokine profiles to a type 1 inflammatory response in C3H/HeJ mice but to a protective type 2 response in BALB/c mice. These
cytokine changes appear to be associated with the severe
arthritis in C3H/HeJ mice following injection of M. arthritidis in comparison to the mild disease seen in injected BALB/c mice.