A second host immune response profile was characterized by TNF-a, IL-1b, Il-10, Il-12, IFN-c and IL-5, which increased from the acute phase into convalescence. Interestingly, TNF-a and IL-1b, which are known to co-induce the other's expression, are both involved in chronic inflammatory diseases such as RA, chronic hepatitis B and C infection [23, 29, 30] . Importantly, TNF-a and IL-1b are main contributors to joint pain, which is the major symptom of RA. An internal balance of TNF-a or IL-1b levels is imperative as mis-regulation of either has been shown to be a major proponent of chronic diseases (RA). Our data indicated that these cytokines increased significantly during patient convalescence above those of the control group, but were not statistically changed in patients reporting mild or severe symptoms. These data may imply that the increased levels of TNF-a and IL-1b in the convalescence phase were not a major contributor of chronic damage causing persistent severe joint pain symptoms during the Italian outbreak even though these cytokines have previously been found to play a destructive role in chronic inflammatory diseases. Furthermore, TNF-a immunomodulators have previously been used as a common treatment for RA and IL-1b immunomodulators are effective with other chronic diseases such as systemiconset juvenile idiopathic arthritis and in adult onset Still's diseases [29, 31] . Taken together, these findings suggest TNF-a and IL-1b therapies would not be effective controlling the prolonged symptoms of CHIKV disease since the raised levels during convalescence were not associated with patient severity. Previously, cytokine profiles have been analyzed from patients during an Asian outbreak of CHIKV [22] . Ng and colleagues, investigated 30 cytokines and growth factors from 10 acute phase CHIKV patients, determined that the levels of 8 cytokines, 2 chemokines and 3 growth factors were significantly raised in patients compared to those of the control group. In accordance with their data, IL-6, CXCL9 and CXCL10 were also increased in the acute phase of our patients as compared to control. Since the results from the previous study did not follow the patients during convalescence, our study added significant insight to the progression of CHIKV disease. We found that these three cytokine levels decreased as the patients convalesced as discussed above. Conversely, we found CCL2 also to be increased in the acute phase compared to that of the control group, which was unchanged in the Ng study. Furthermore, Ng et al. found IL-5 and IL-10 were significantly increased in the acute phase where our data indicated that IL-5 and IL-10 were initially low and below control levels and increased following the acute phase. These discrepancies can possibly be explained by the patient populations: the Ng study patients and our patients were from significantly varied genetic backgrounds (Asian and European, respectively). Therefore, differences in immune response may reflect variations in immunological genetic programs. As well, the virus that caused the two outbreaks also differed genetically. Even though the virus that caused the Singapore outbreak was the same genotype as the Italian virus, the virus that infected the Italian patients had the A226V mutation in the E1 gene which was acquired on La Reunion Island [19] . Although the impact of this mutation has been shown to increase vector infectivity [20] , the mutation has not been investigated on the human or mammalian immune response.