The Effect of Minocycline in Rat Models of Inflammatory Arthritis: Correlation of Arthritis Suppression with Enhanced T Cell Calcium Flux

Adjuvant and collagen arthritis in the rat are widely accepted T-cell-dependent counterparts of rheumatoid arthritis and were used to examine the antiinflammatory properties of minocycline. Administration of oral minocycline, a semisynthetic tetracycline, significantly decreased (P< 0.01) the incidence of arthritis in both models.In vivoexposure to minocycline also significantly increased the percentage of splenocytes exhibiting a rise in free intracellular calcium concentration ([Ca2+]i) following concanavalin A stimulation (P< 0.05 in adjuvant andP< 0.01 in collagen). This enhancement was mitogen dose-dependent and supported exclusively by extracellular Ca2+. Resting [Ca2+]ilevels were unaffected by minocycline and predominantly the CD4+subset was involved. No changes were observed in weight, IgG antibodies to collagen, synoviocyte release of collagenase and prostaglandin E2, acute inflammation in an air-pouch system, or cell surface expression of activation markers (interleukin-2 and transferrin receptors) by splenocytes or lymph node cells. As a controlled [Ca2+]irise is a critical event in normal T cell activation, minocyclineʹs antiarthritic profilein vivomay relate to perturbed Ca2+influx during T cell activation, an alteration that could promote the development of clinical tolerance to otherwise arthritogenic stimuli.