Both patient groups demonstrate in spite of a much higher expression of TNFa within cartilage of the TNFaHi- phenotype compared to IL-1b in the cartilage of the TNFaLo-phenotype equivalent grades of cartilage destruction, demonstrating the higher biologic activity of IL-1b. Since activated chondrocytes are able to express all the cytokines and growth factors known to be involved in cartilage metabolism, they seem to participate actively in the pathogenesis of OA. Most cytokines and growth factors were detected in the middle to deep layers of OA-cartilage and the exclusive location of IGF I in the superficial layers of the tissue was the only exception.

We were able to confirm a bilateral stimulation of TNFa_and IL-6 on the one hand and of_IL-1b, IL-4, IL-10 and TGFb1 on the other hand. IL-4, IL-10 and TGFb1 reduced the amount of IL-6 synthesized and TNFa was able to inhibit the synthesis of cytokines characteristic of the TNFaLo-phenotype.

For both phenotypes an association with distinct genotypes was found: the TNFaLo-phenotype revealed a statistically significant association with alleles 2 of IL-1b leading to the characteristic enhancement of IL-1b-expression, as well as of IL-6 which causes a reduction of IL-6 secretion. In contrast to that we were able to confirm a statistic significant correlation of allele 2 of IL-1 receptor antagonist (IL-1Ra), responsible for an enhanced expression of the antagonist, with the TNFaHi-phenotype. Our data demonstrate that genes coding for IL-1Ra, IL-1b and IL-6 and their gene products that contribute to the balance between synthesis and degradation of articular cartilage, could have an important influence on the development of OA.