It is likely that this early antibody response was preceded by an intense early Th2 cytokine up regulation. However, a large number of patients with typical acute illness and intense Th1 and Th2 cytokine response did not test seropositive for anti CHIKV antibodies and needs to be investigated further. Rapid induction of type I interferon expression is critical to stimulating a robust innate immune response against viral infection and requires the activation of multiple transcriptional proteins following engagement and signaling through Toll-like receptor-dependent and independent pathways. Alpha viruses, like several other viruses are potent inducers of interferon which in turn inhibits viral replication. Gifford and Heller reported for the first time during the 1954–1964 CHIKV epidemic in Asia and South India, that chick embryo fibroblasts infected with CHIKV produced detectable levels of type 1 interferon three hours after infection. Macrophages, a major source of interferon, are readily infected by CHIKV and play a pivotal role in several cellular responses shown in experimental studies and in both Th1 and Th2 cytokine response. Based on the observation of a sharp decline in viraemia before the appearance of high-affinity neutralizing antibodies, it was hypothesized that type 1 IFNs mediate antiviral response. Type II IFN produced in early CHIKV infection further promotes the transition from innate to adaptive immunity. An earlier study had shown that CHIKV-specific CD4+ T cells induced by CHIKV infection were the major producers of IFN- c and that Th1 cells were probably responsible for a skewed production of IgG2 antibodies by B cells in response to IFN- c. IFN-gamma is made exclusively by natural killer and T cells and has important immunoregulatory functions including intense stimulation of macrophages, monocytes, fibroblasts and dendritic cells. AZ 960 905586-69-8 Pro-inflammatory mediators including TNF-a, MCP-1, IFN- c, IFN- a/b and IL-6 have been identified in primates and humans infected with CHIKV and in other alphaviral arthritides. Immunological studies on muscle biopsies from CHIKV infected patients with myositis syndrome showed presence of viral antigens located exclusively inside skeletal muscle progenitor cells and not in muscle fibres. Though pathophysiologically, the intense and conjoint upregulation of Th1 and Th2 cytokines definitely contribute to the severe but self limiting profile of painful inflammatory pattern of the musculoskeletal illness in CHIKV, the literature is silent on the individual contribution of cytokines towards the clinical phenotype. In this report we have attempted to describe interesting and plausible clinical, laboratory and serological correlations of the up-regulated cytokines. To the best of our knowledge, this is the first report to describe IL-13 responses in acute CHIKV. While IFN – c, TNF- a and CXCL-10/IP-10 are pro-inflammatory and a hallmark of Th1 response.