In IFNB treated patients, on the other hand, the IL6 pathway in women but the IFN pathway in men were responsible for delay ing EDSS. In recent studies, looking at the role of sCD30 in immunological and neurological pathways, we noted that the down or up regulation of sCD30 levels respect ively linked to the up or down regulation selleck Sunitinib of TGFB levels, within physiological or pathological ranges, repre sented a dual biomarker for homeostasis or imbalance in immunological and neurological pathways and hence for the success or failure of IFNB treatment. On this basis, one of our most important findings was that CD30 path ways are re established we found that a fall in the level of sCD30 is linked to an increase in TGFB levels in both treated patient sex groups compared to untreated patient sex groups.

Hence, sCD30 levels linked to TGFB levels can be used as a dual gender target and biomarker in both sexes to evaluate the success of IFNB therapy in terms Inhibitors,Modulators,Libraries of re establishment of Th network balance and the delay of the progression of neurological disability. Furthermore Inhibitors,Modulators,Libraries it is possible to evaluate gender specific success of therapy by looking at the positive linked relationships between cytokine levels of IL6 IL4 and IFN IL10 in men, while the negative one between IL6 IL10 and the positive ones between IL2 IL4, IL6 IFN in women. Overall, our findings underline the need for gender specific drugs that take into account the differing regula tion of the immune response whilst ensuring the same result a physiological homeostasis in the resting state, in the transition to the activation phase and in the return to the resting state.

Obviously these regulatory differ ences do not usually have consequences until pathway alterations Inhibitors,Modulators,Libraries Inhibitors,Modulators,Libraries occur. In fact, it is well known that in health, in both sexes, the immune system carries out its responses and recovers its initial homeostasis, regard less of differing initial conditions or evolution. If, how ever, these alterations occur in IFN andor IL6 cytokine pathways, the consequences for men and women, in terms of pathological mechanisms and disease develop ment, are different. The malfunctioning of gender Inhibitors,Modulators,Libraries specific pathways not only compromises the homeostasis of the immune response, but may also cause a pathological polarization of T cell subsets specific to each sex IFN supports the development of Th1 func tions promoting cell mediated immunity, while IL6 cytokine supports Th2 responses where B lymphocytes are activated and antibody production flourishes.

In fact, IFN and IL 6 cytokines were initially Tipifarnib cost classified as the cytokines responsible for generating Th1 and Th2 type immune responses respectively. Research in this field, however, has shown that it is not a single cytokine that determines a particular response, but rather the interaction of indi vidual cytokines within a network.