Persistent Arthralgia Induced by Chikungunya Virus Infection is Associated with Interleukin-6 and Granulocyte Macrophage Colony-Stimulating Factor

Abstract

Background. Chikungunya virus (CHIKV) infection induces arthralgia. The involvement of inflammatory cytokines and chemokines has been suggested, but very little is known about their secretion profile in CHIKV-infected patients.Methods. A case-control longitudinal study was performed that involved 30 adult patients with laboratory-confirmed Chikungunya fever. Their profiles of clinical disease, viral load, and immune mediators were investigated.Results. When patients were segregated into high viral load and low viral load groups during the acute phase, those with high viremia had lymphopenia, lower levels of monocytes, neutrophilia, and signs of inflammation. The high viral load group was also characterized by a higher production of pro-inflammatory cytokines, such as interferon-α and interleukin (IL)–6, during the acute phase. As the disease progressed to the chronic phase, IL-17 became detectable. However, persistent arthralgia was associated with higher levels of IL-6 and granulocyte macrophage colony-stimulating factor, whereas patients who recovered fully had high levels of Eotaxin and hepatocyte growth factor.Conclusions. The level of CHIKV viremia during the acute phase determined specific patterns of pro-inflammatory cytokines, which were associated with disease severity. At the chronic phase, levels of IL-6, and granulocyte macrophage colony-stimulating factor found to be associated with persistent arthralgia provide a possible explanation for the etiology of arthralgia that plagues numerous CHIKV-infected patients.

Arthrogenic Alphaviruses and Inflammatory Myopathies

“…Similarly, studies on human SINV infection with Pogosta disease mainly involved analysis of human serum for antibody and viral antigen detection. Human CHIKV infection has been clinically well documented (Chow et al, 2011;Pialoux et al, 2007;Powers & Logue, 2007;Simon et al, 2007;Sissoko et al, 2010;Taubitz et al, 2007). The serology profile during the course of infection has been documented by numerous studies, showing that viraemia lasts 5-7 days (acute infection), with a subsequent IgM+/IgG-sub-acute infection progressing for a further week until IgG antibodies are detected and in some cases IgM was still detectable (Staikowsky et al, 2009).…”

“…Of particular interest is the upregulation of IL-6, TNF-, IL-1, IFN-, interferon-inducible protein-10 (IP-10) and monokine induced by IFN- (MIG) (Hoarau et al, 2010;Ng et al, 2009b). There has been an association between high levels of viraemia in acute CHIKV-infected patients and a higher production of pro-inflammatory cytokines such as IL-6 and TNF- (Chow et al, 2011). Presentation of chronic disease symptoms has also been associated with elevated levels of IL-6 and granulocyte macrophage colony-stimulating factor (GM-CSF) (Chow et al, 2011).…”

“…There has been an association between high levels of viraemia in acute CHIKV-infected patients and a higher production of pro-inflammatory cytokines such as IL-6 and TNF- (Chow et al, 2011). Presentation of chronic disease symptoms has also been associated with elevated levels of IL-6 and granulocyte macrophage colony-stimulating factor (GM-CSF) (Chow et al, 2011). Whereas in patients who have fully recovered from disease, high levels of eotaxin and hepatocyte growth factor have been detected (Chow et al, 2011).…”

“…Presentation of chronic disease symptoms has also been associated with elevated levels of IL-6 and granulocyte macrophage colony-stimulating factor (GM-CSF) (Chow et al, 2011). Whereas in patients who have fully recovered from disease, high levels of eotaxin and hepatocyte growth factor have been detected (Chow et al, 2011). Analysis of pro-inflammatory mediators in an adult C57BL/6 mouse model of CHIKV disease revealed an up-regulation in the expression of TNF-, MCP-1, IFN-, IL-6 and IFN-/ in the sera of infected mice (Gardner et al, 2010).…”

Chikungunya and Its Interaction With the Host Cell

“…Cytokines may also contribute to chronic CHIKV disease, as persistent arthralgia has been associated with elevated levels of IL-6 and granulocyte-macrophage colony-stimulating factor (GM-CSF) [83]. Several studies have tried to identify the factors associated with chronic Chikungunya disease in groups of patients in Singapore [83], La Réunion [84], Dakshina Kannada (India) [85,86], and Emilia Romagna (Italy) [87].…”