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Infection and Immunity, March 2000, p. 1142-1149, Vol. 68, No. 3
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Modulation of Cytokine Profiles by the Mycoplasma Superantigen Mycoplasma arthritidis Mitogen Parallels Susceptibility to Arthritis Induced by M. arthritidis

Hong-Hua Mu,* Allen D. Sawitzke, and Barry C. Cole*

Division of Rheumatology, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, Utah 84132

Received 20 August 1999/Returned for modification 3 November 1999/Accepted 30 November 1999

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.


* Corresponding author. Mailing address: Division of Rheumatology, Department of Internal Medicine, University of Utah School of Medicine, 50 N. Medical Dr., Salt Lake City, UT 84132. Phone: (801) 581-8845. Fax: (801) 581-6069. E-mail for Hong-Hua Mu: hong.mu{at}m.cc.utah.edu. E-mail for Barry C. Cole: barry.cole{at}hsc.utah.edu.


Infection and Immunity, March 2000, p. 1142-1149, Vol. 68, No. 3
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.



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