Modulation of cytokine profiles by the mycoplasma superantigen Mycoplasma arthritidis mitogen parallels susceptibility to arthritis induced by M-arthritidis

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 C3 H/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 prof iles were seen irrespective of the MAM dose. However, there were striking d ifferences 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 th e most marked divergence in the secreted cytokines. Type 1 cytokines were m arkedly elevated in C3H/HeJ cell supernatants, whereas they were depressed or remained law in BALB/c cell supernatants. In contrast, the levels of typ e 2 cytokines were all greatly increased in BALB/c cell cultures but were d ecreased or remained low in C3H/HeJ supernatants. Interleukin-12 mRNA and p rotein was also markedly elevated in C3H/HeJ mice, as were the levels of im munoglobulin G2a. The data indicate a major skewing in cytokine profiles to a type I inflammatory response in C3H/HeJ mice but to a protective type 2 response in BALB/c mice. These cytokine changes appear to be associated,vit h the severe arthritis in C3H/HeJ mice following injection of M. arthritidi s in comparison to the mild disease seen in injected BALB/c mice.