Autoimmune response in MRL+/+ mice following treatment with dichloroacetyl chloride or dichloroacetic anhydride

Journal Article · Sun Oct 15 04:00:00 EDT 2006 · Toxicology and Applied Pharmacology

OSTI ID:20850445

Ping, Cai ^[1]; Koenig, Rolf ^[2]; Khan, M Firoze ^[1]; Qiu, Suimin ^[1]; Kaphalia, Bhupendra S ^[1]; Ansari, G A.S. . ^[1]

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1. Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555-0609 (United States)
2. Department of Microbiology and Immununology, University of Texas Medical Branch, Galveston, TX 77555 (United States)

Dichloroacetyl chloride (DCAC) is formed from trichloroethene (TCE), which is implicated in inducing/accelerating autoimmune response. Due to its potent acylating activity, DCAC may convert proteins to neo-antigens and thus could induce autoimmune responses. Dichloroacetic anhydride (DCAA), which is a similar acylating agent, might also induce autoimmune responses. To evaluate if chloroacylation plays a role in the induction of autoimmunity, we have measured the autoimmune responses following treatment with DCAC or DCAA in autoimmune-prone MRL+/+ mice. Five-week-old female mice were injected intraperitoneally (twice weekly) with 0.2 mmol/kg of DCAC or DCAA in corn oil for 6 weeks. Total serum IgG, IgG1, and IgE levels were significantly increased in DCAC-treated mice as compared to controls. These increases corresponded with increases in DCAC-specific IgG and IgG1 levels. Total serum IgM was decreased in both DCAC- and DCAA-treated mice. Antinuclear antibodies, measured as an indication of systemic autoimmune responses, were increased in both DCAC- and DCAA-treated mice. Of eight Th1/Th2 cytokines measured in the serum, only IL-5 was significantly decreased in both treatment groups. The cytokine secretion patterns of splenic lymphocytes after stimulation with antibodies against CD3 (T cell receptor-mediated signal) and CD28 (costimulatory signal) differed between treatment and control groups. Levels of IL-1, IL-3, IL-6, IFN-{gamma}, G-CSF, and KC were higher in cultures of stimulated splenocytes from either DCAC- or DCAA-treated mice than from controls. The level of IL-17 was only increased in cultures from DCAC-treated mice. Increased lymphocytic populations were found in the red pulp of spleens following treatment with either DCAC or DCAA. In addition, thickening of the alveolar septa in the lungs of DCAC- or DCAA-treated mice was observed. The lung histopathology in exposed mice was consistent with the symptomology observed in welders exposed to DCAC/phosgene. Thickening was more pronounced in DCAC-treated mice. Our data suggest that DCAC and DCAA elicit autoimmune responses in MRL+/+ mice that might be reflective of their chloroacylation potential in vivo.

• OSTI ID: 20850445
• Journal Information: Toxicology and Applied Pharmacology, Journal Name: Toxicology and Applied Pharmacology Journal Issue: 2 Vol. 216; ISSN TXAPA9; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ANHYDRIDES
ANTIBODIES
ANTIGENS
CHLORIDES
CORN OIL
IN VIVO
LUNGS
LYMPHOCYTES
LYMPHOKINES
MICE
PHOSGENE
RECEPTORS
SECRETION
SPLEEN