Heavy metal exposure reverses genetic resistance to Chlamydia-induced arthritis.
BACKGROUND
We have previously observed that Brown Norway (BN) rats display a relative resistance to experimental Chlamydia-induced arthritis. In the present study, we examine an environmental toxin, mercuric chloride (HgCl2), as a modulator of this innate resistance to arthritis.


METHODS
To assess the effect of the heavy metal exposure, one group of rats received two subcutaneous injections of HgCl2 (1 mg/kg) 48 hours apart. Seven days later, the animals received the intra-articular injection of synoviocyte-packaged Chlamydia.


RESULTS
Histopathology revealed that BN rats receiving only Chlamydia had a minimal cellular infiltration in the joint, which was predominantly mononuclear in character. In contrast, mercury-exposed rats had a marked exacerbation of the histopathological severity of the arthritis, and the infiltration was predominantly neutrophilic. Mercury exposure was also associated with marked enhancement in IgE levels and an alteration in IgG2a/IgG1 ratio, reflecting a Th2 shift. The local cytokine profile in the joint was markedly altered after mercury exposure, with a suppression of tumour necrosis factor-alpha and interferon-gamma but an enhancement of vascular endothelial growth factor. This was associated with decreased host clearance capacity reflected in enhanced bacterial load in both the spleen and the joint and was accompanied by enhanced detection of microbial antigens in the synovial tissues by immunohistological staining.


CONCLUSIONS
Genetically defined cytokine production in the joint defines the severity of reactive arthritis by dictating the local clearance of the pathogen. This interplay can be altered dramatically by heavy metal exposure, which results in suppression of protective cytokines in the microenvironment of the joint.
Inman
Robert D
RD
Division of Genes and Development, Toronto Western Research Institute, 399 Bathurst Street, Toronto, ON M5T2S8, Canada. robert.inman@uhn.on.ca
Chiu
Basil
B
D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001169:Arthritis, Experimental / Q000235:genetics* / Q000276:immunology; D016918:Arthritis, Reactive / Q000235:genetics*; D002690:Chlamydia Infections / Q000150:complications* / Q000276:immunology; D024043:Collagen Type II / Q000097:blood; D016207:Cytokines / Q000032:analysis / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D007719:Knee Joint / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008297:Male; D008627:Mercuric Chloride / Q000633:toxicity*; D051381:Rats
D000907:Antibodies, Bacterial; D024043:Collagen Type II; D016207:Cytokines; D007073:Immunoglobulin E; D008627:Mercuric Chloride