Susceptibility to adjuvant arthritis: relative importance of adrenal activity and bacterial flora

Abstract

SUMMARYPrevious studies on the regulation of bacterial-induced arthritis in rats have focused on endocrine aspects as well as differences in T cell immunity against bacterial epitopes. We analysed the role of both adrenal activity and bacterial flora in determining susceptibility to baclerial-induced arthritis. Outbred Wistar rats show a low incidence of adjuvant arthritis. Moderate sensitivity to adjuvant arthritis was found in a selected., stress-resist ant line of the Wistar rat, whereas no arthritis was found in a stress-susceptible Wistar line. Plasma corticosterone responses after IL-la exposure were, however, identical in these two lines, excluding a direct correlation between susceptibility and corticosterone levels. In line with previous findings in germ-free (GF) F344 rats, GE Wistars also appeared highly susceptible to arthritis. We further analysed the corticosterone responses in GE and conventional (CV) rats. Administration of IL-l^ induced identical corticosterone responses in both CV and GF E344 rats. In addition, plasma corticosterone levels were measured around the time of onset of arthritis. Whereas no rise was seen in the arthritis-resistant CV rats, a significant increase was observed from day 14 in GE rats, at the moment of onset of arthritis. Although this corticosterone response was insufficient to prevent arthritis, it may have ameliorated disease expression in the GK F344 rats. Our data indicate that the bacterial flora, and therefore T cell tolerance, is of prime importance in determining susceptibility, whereas the activity of the hypothalamus-pituitary-adrenal (HPA) axis may modulate disease severity.

Ellagic acid alleviates adjuvant induced arthritis by modulation of pro- and anti-inflammatory cytokines

“…The synovial membrane becomes hyperplastic and extends to form villi. The osteoclast-rich portion of the synovial membrane, or pannus, destroys bone whereas enzymes secreted by neutrophils, synoviocytes, and chondrocytes degrade cartilage [47–49]. Histopathological investigations of this study showed slight cartilage destruction, bone resorption, periosteal proliferation, and marked synovitis, as well as periarticular inflammation in arthritic untreated mice.…”

The determinants of susceptibility/resistance to adjuvant arthritis in rats

“…With regard to behavior of rat strains and arthritis susceptibility, experiments in different rat strains (DA rats, LEW rats, AO rats, PVG rats, outbred Wistar rats) indicated that the development of arthritis and severity of the disease upon Mtb injection correlated well with specific behavioral patterns of the rat strains [ 55 ]. A study comparing apomorphine-susceptible versus apomorphine-unsusceptible Wistar rats showed that the former were relatively resistant to AA, whereas the latter developed arthritis of moderate severity [ 56 ]. In another study, Wistar rats were separated into two groups based on their learned helplessness (which also forms the basis for an animal model of depression), and were then immunized with Mtb [ 57 ].…”

“…Additional mechanisms might also contribute to the acquired AA resistance in F344 rats, however, including tolerance induction in the subset of T cells directed against hsp65 and the pathogenic epitope of Bhsp65, bystander activation of T cells, effects of a superantigen, a differential HPA axis response at the onset of arthritis (with germ-free F344 rats but not conventional F344 rats showing an increase in plasma corticosterone) [ 56 ], and an alteration of the T-cell effector/T-cell regulatory balance by gut flora DNA [ 59 , 61 ]. It has been shown that interaction of gut flora DNA with TLR9 influences immune homeostasis in the intestine.…”

The roles of the hypothalamus and the gastrointestinal tract in the prevention of inflammatory autoimmune disease

“…In a study by van de Langerijt and colleagues in a recent issue [29], experiments are described to evaluate the relative importance of inflammation-induced cortieosteroid release and of diversity in the intestinal bacterial flora in the control of an experimental autoimmune disease, adjuvant-induced arthritis. Using difl"erent strains of rats varying in their stress response and ones from germ-free or conventional environments the authors concluded that the diversity ofthe bacterial flora was of the greater significance in determining disease susceptibility, while the stress response modulated the severity of disease.…”