Effects of a novel anti-inflammatory retinoid-like 2,4,6,8-nonatetraenoic acid on the immunological changes associated with adjuvant-induced arthritis.

Proliferative responses to the T-cell mitogen, Con A, were markedly suppressed in spleen cells isolated from rats 12-16 days following induction of adjuvant-induced arthritis (AA). These responses were only partially restored following removal of plastic-adherent cells (AC-depleted). Prophylactic treatment of AA rats with a novel anti-inflammatory retinoid-like 2,4,6,8-nonatetraenoic acid, Ro 23-6457, increased mitogen-induced proliferative responses in spleen cells, particularly in AC-depleted cultures. Treatment of AA rats with Ro 23-6457 significantly increased Con A-induced IL-2 production by both unseparated and AC-depleted spleen cells. Although exogenous IL-2 did not restore proliferative responses to Con A-stimulated spleen cells from vehicle-treated AA rats, responses in AC-depleted cells from Ro 23-6457-treated AA rats were further enhanced by the addition of IL-2. Following stimulation with LPS, supernatants from cultures of adherent spleen cells isolated from AA rats contained more IL-1 (expressed as units/ml) than cultures from normal rats. Treatment of AA rats with a high dose of Ro 23-6457 normalised IL-1 levels in these cultures. Treatment of normal rats with Ro 23-6457 had no significant effects on any parameter tested. These data suggest that Ro 23-6457's modulation of certain disease-associated alterations in immune function in AA rats may contribute to its anti-inflammatory activity.