Th1/Th2 cytokine gene expression after mercuric chloride in susceptible and resistant rat strains.
Mercuric chloride (HgCl2) has contrasting effects on different rat strains: susceptible strains, e.g. Brown Norway (BN) develop polyclonal B cell activation, multiple autoantibodies and widespread tissue injury. Lewis (LEW) rats are resistant: no autoimmune response occurs after HgCl2; instead, there is immunosuppression. We have previously shown, by fully quantitative polymerase chain reaction (PCR), up-regulation of interleukin-4 (IL-4) gene expression in HgCl2-treated BN rats, implicating Th2 cells in the autoimmune syndrome. Involvement of the reciprocal Th1 subset, producing interferon-gamma (IFN-gamma), in resistance of LEW rats to HgCl2 has been suggested. We now report extensive analysis of Th1 and Th2 cytokine gene expression in spleen and lymph nodes of susceptible (BN) and resistant (LEW) rats after HgCl2. IL-4 and IFN-gamma were analyzed by quantitative PCR, other cytokines were assessed using semiquantitative PCR: the relative merits of these two techniques are discussed. We show pronounced up-regulation of IL-4 and more modest up-regulation of IFN-gamma in BN rats, but no up-regulation of either in LEW rats. Baseline levels of IFN-gamma were higher in Lew rats. Semiquantitative PCR showed increased expression of IL-2, IL-6 and IL-10 in BN; in LEW rats only IL-10 was increased. There was no marked change in IL-5, IL-13 or transforming growth factor-beta (TGF-beta) in either strain. These data further support the key role of IL-4 in HgCl2-induced autoimmunity, and suggest that failure of up-regulation of IL-4, together with higher baseline IFN-gamma expression, accounts for resistance of LEW rats to HgCl2. However, neither IFN-gamma nor TGF-beta can be implicated in HgCl2-induced immunosuppression in the LEW rat in vivo: our data suggest a role for IL-10 in this phenomenon.
Department of Medicine, University of Bristol, GB.
K M
KM
Gillespie
A
A
Saoudi
J
J
Kuhn
C J
CJ
Whittle
P
P
Druet
B
B
Bellon
P W
PW
Mathieson
D000818:Animals; D001327:Autoimmune Diseases / Q000139:chemically induced* / Q000235:genetics; D016207:Cytokines / Q000235:genetics*; D005786:Gene Expression Regulation; D007371:Interferon-gamma / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics; D008198:Lymph Nodes / Q000502:physiology; D008627:Mercuric Chloride / Q000494:pharmacology*; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
D016207:Cytokines; D015847:Interleukin-4; D008627:Mercuric Chloride; D007371:Interferon-gamma