Altered circulating levels of matrix metalloproteinases and inhibitors associated with elevated type 2 cytokines in lymphatic filarial disease

Background: infection with wuchereria bancrofti can cause severe disease characterized by subcutaneous fibrosis and extracellular matrix remodeling. matrix metalloproteinases (mmps) are a family of enzymes governing extracellular remodeling by regulating cellular homeostasis,inflammation,and tissue reorganization,while tissue-inhibitors of metalloproteinases (timps) are endogenous regulators of mmps. homeostatic as well as inflammation-induced balance between mmps and timps is considered critical in mediating tissue pathology. methods: to elucidate the role of mmps and timps in filarial pathology,we compared the plasma levels of a panel of mmps,timps,other pro-fibrotic factors,and cytokines in individuals with chronic filarial pathology with (cp ag+) or without (cp ag-) active infection to those with clinically asymptomatic infections (inf) and in those without infection (endemic normal [en]). markers of pathogenesis were delineated based on comparisons between the two actively infected groups (cp ag+ compared to inf) and those without active infection (cp ag- compared to en). results and conclusion: our data reveal that an increase in circulating levels of mmps and timps is characteristic of the filarial disease process per se and not of active infection; however,filarial disease with active infection is specifically associated with increased ratios of mmp1/timp4 and mmp8/timp4 as well as with pro-fibrotic cytokines (il-5,il-13 and tgf-β). our data therefore suggest that while filarial lymphatic disease is characterized by a non-specific increase in plasma mmps and timps,the balance between mmps and timps is an important factor in regulating tissue pathology during active infection.