EFFECTS OF CYCLOPHOSPHAMIDE (ENDOXAN) IN EXPERIMENTAL ARTHRITIS OF RABBITS

  • 1 January 1978
    • journal article
    • research article
    • Vol. 37  (5-6) , 174-199
Abstract
Cyclophosphamide (Cp) in different dosages was well tolerated locally when injected into the knee joint of normal rabbits as compared to saline controls on the basis of histology and cell count determination of the injected joints. A hyperimmune arthritis (HIA) was produced in rabbits by systemic administration of albumin, complete Freund''s adjuvant and intraarticular stimulus by ovalbumin. Histological examination of synovial membranes reveal alterations similar to those of human rheumatoid arthritis on the 7th day after stimulus. Further experiments were aimed at assessing if Cp exerted an inhibitory effect on the 7 day old HIA. Cp in a dosage of 10 mg was applied intraarticularly in various intervals prior, simultaneously and after the elicitation of HIA. Cp led to a reduction of the number of lymphocytes, plasma cells and fibroblasts in the synovial membrane. The inhibitory effect on fibroblasts was bound to its administration around the point of HIA elicitation. An even stronger inhibition of lymphocytes and plasma cells was only to be expected when Cp was applied 48 h after ovalbumin challenge. Unwanted reactions in the course of Cp administration such as superficial and deep necrosis as well as damage of blood vessels in the synovial membrane combined with minor inhibition of lymphocytes and plasma cells were encountered when Cp was injected 120 h after HIA elicitation. Efficacy and unwanted reactions during Cp administration are related to a local activation of the substance in the inflammatory milieu of HIA. The sole application of Cp, if injected shortly before immigration of lymphocytes into synovial tissue, led to a marked suppression of almost all histological parameters of HIA. The experimental findings support the importance of lymphocytes and plasma cells being inactivated for the successful treatment of adult rheumatoid arthritis. The formation of necrosis and damage of blood vessels may be sequelae of too fast a local activation of Cp in the inflammatory tissue.