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Infection and Immunity, March 2000, p. 1142-1149, Vol. 68, No. 3
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.
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
*
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.
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