Suppression of adjuvant‐induced arthritis in da rats by incomplete freund's adjuvant

Abstract

Objective. To define the effects of incomplete Freund's adjuvant (LCFA) on subsequent arthritis induced by complete Freund's adjuvant (CFA) and type I1 collagen (CII) in DA and Lewis rats.Methods. ICFA was injected into DA and Lewis rats before CFA or CII injection.Results. DA rats previously injected with ICFA had significantly less severe arthritis induced by CFA compared with those not receiving ICFA pretreatment (P < 0.01). ICFA had no significant impact on CFAinduced arthritis in Lewis rats or on CII-induced arthritis in DA rats.Conclusion. The injection of ICFA alone specifically suppresses subsequent CFA-induced arthritis in DA rats, but not in Lewis rats. DA rats injected with incomplete MATERIALS AND METHODSAnimals. All procedures involving animals were approved by the institutional animal care and use committees of the University of Utah and the VA Medical Center. DA rats from Bantin and Kingman (Fremont, CA), DA rats bred in facilities at the University of Utah, and Lewis rats from Harlan Sprague Dawley (Indianapolis, IN) were used. All animals were male and were 8-12 weeks old at the time of study.Injections of incomplete and complete Freund's adjuvant. ICFA (Difco, Detroit, MI) was administered as 0.1 ml injected intradermally at the base of the tail (1-3). The same lot of ICFA was used in experiments 1,2, and 3. During each of experiments 4,5, and 6, different lots of ICFA were used. CFA was prepared by mixing Mycobucterium butyricum (Difco) and ICFA at a concentration 7.5 mg/ml. CFA injections (0.1 ml) were administered intradermally at the base of the tail.Induction of collagen-induced arthritis. Porcine type I1 collagen (CII) was prepared for injection as previously described (4). Briefly, CII was suspended in 0.1M acetic acid at 1 mglml and emulsified in an equal volume of ICFA (Difco) to give a final concentration of 0.5 mg/ml of CII in the emulsion of acetic acid and ICFA. Rats were injected intradermally on the back with 2 mg/kg CII. Arthritis evaluation. An observer who was blinded to the previous treatment evaluated the animals daily for the onset of arthritis and assessed the severity of arthritis twice weekly, as previously described (1-3). The severity of arthritis in the wrist, mid-forepaw, mid-hindpaw, and ankle joints was scored as 0 = no arthritis, 1 = extreme redness and/or minimal swelling, 2 = moderate swelling, 3 = severe swelling, and 4 = severe swelling and inability to bear weight. The presence or absence of arthritis in the interphalangeal, metacarpophalangeal, and metatarsophalangeal

Oligodeoxynucleotides containing CpG motifs can induce T cell–dependent arthritis in rats

“…No sex differences in degree of joint inflammation and disease course were observed. In rats of the DA strain, several substances with known arthritogenic effects, including IFA, can induce severe arthritis (15,24,25). Injection of IFA with CpG added did not increase the disease severity compared with IFA alone, and CpG administered in PBS did not induce disease in the DA rat.…”

Arthritis induced in rats with non‐immunogenic adjuvants as models for rheumatoid arthritis

“…Many other rat strains have been tested for disease susceptibility and were found to vary dramatically. Most strains are resistant to OIA and only the DA and the DXEA strains develop a mild acute arthritis (33,34,40). The DXEA strain contains DA genes since it is a recombinant inbred of E3 and DA.…”

“…The role of the MHC region in many of these models (OIA, AvIA, PIA and SIA) has been addressed using already established congenic strains on the LEW or DA background as well as in F2 crosses (6,33,40,78,92). Thus, studies of PIA have confirmed an MHC association (denoted Pia1) in both congenic strains and F2 crosses (6,92).…”

“…It should thus be possible to identify genetic loci associated with disease susceptibility by analyzing progeny from the F2 generation or from backcrosses between susceptible and resistant rat strains. Based on experiments with MHC congenic DA rat strains, it was reported that the MHC haplotypes RT1n (33) and RT1h (40) that non-MHC genes in the DA rat determine arthritis development, since LEW.1AV1 and PVG.1AV1 rats are resistant although they share the congenic fragment with the RT1av1 haplotype (40, 100). To map the chromosomal location of susceptibility genes, a genome-wide linkage analysis was performed, employing progeny from a (DAxLEW.1AV1)F2 intercross (101).…”

“…This oil-induced arthritis developed also in germ-free DA rats, demonstrating that microorganisms are not involved in the pathogenesis and that responses to heat shock proteins did not occur in the germfree rats (32). However, most other rat strains, including the LEW (Lewis) strain, which is highly susceptible to MIA, was resistant to mineral oil-induced arthritis (OIA) (31,33,34). Taken together, these data infer that the mycobacterial component and the oil cause arthritis by separate mechanisms.…”