Relationships between the activity of MMP1/TIMP1 enzymes and the TH1/TH2 cytokine network

The evaluation of the balance between matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) would appear to be importan t in cancer patients. Since the activity of these enzymes is regulated at t he gene level by cytokines, we studied the Serum relationships between MMP1 /TIMP1 and the network of TH1/TH2 cytokines in healthy subjects to better u nderstand how the physiological network of cytokines regulates MMP1/TIMP1 a ctivity. Such a study could lead to suggestions for follow-up experiments t o create prognostic and diagnostic indices for more efficient disease preve ntion programs and biotherapeutic treatments of patients. Far this purpose, we determined serum levels of MMP1, TIMP1 and interleukin (IL)2, interfero n (IFN) gamma, IL4 and IL10 in both healthy men and women (men and women we re analyzed separately as hormones are one of the non-cytokine regulatory f actors of TH1 or TH2 polarization). These cytokines make up our basic netwo rk. Cytokines within the physiological network function simultaneously so m athematical models of multivariate statistical methods were used to study M P1/TIMP1 and TH1/TH2 network relationships. It has been suggested that math ematical modeling is the only effective way of studying the immune system a s a whole. The influence of network activation, antigen presenting cells, a ntibody response and chemokines on MMP1/TIMP1 balance was also studied. Net work activation was evaluated by measuring the levels of soluble IL2 recept ors (sIL2R) and sIL6R; the influence of antigen presenting cells was evalua ted by measuring serum levels of tumor necrosis factor alpha(TNF alpha) and IL1 beta; antibody response was evaluated by measuring IL5 and IL6 serum l evels and the influence of chemokines was evaluated by measuring serum leve ls of IL8. Our overall results suggest that there are relationships between the activity of MMP1/TIMP1 and the TH1/TH2 network in physiological condit ions. These data may be useful in gaining a clearer insight into how the tw o systems interact and hence regulate the physiological homeostasis. Theref ore, this paper provides suggestions for experimental studies on MMP1/TIMp1 enzymes and TH1/TH2 cytokines to create clinical and prognostic markers fo r patient evaluation.