Chikungunya fever, caused by the chikungunya virus, is a mosquito-borne, infectious disease that is endemic to Southeast Asia and Africa. Patients with chikungunya fever typically experience persistent pain in their joints (arthralgia), but why this happens has so far remained a mystery. Lisa Fong Poh Ng at the A*STAR Singapore Immunology Network and co-workers from the Communicable Diseases Centre (CDC) at Tan Tock Seng Hospital have conducted a longitudinal study on 30 patients with chikungunya fever and found a strong positive correlation between the amount of virus (known as the viral load) present in the body and the level of inflammatory cytokines. The finding could help explain why the majority of patients with chikungunya fever are plagued by persistent arthralgia.
There is not yet a consensus on the pathology of arthralgia in patients with chikungunya fever, but many scientists have postulated that the problem is caused by abnormal immune responses in the body—most likely inflammation promoted by inflammatory cytokines. Ng and co-workers therefore investigated the viral load, key laboratory parameters and cytokine levels in patients with chikungunya fever.
The 30 patients—26 males and four females—were admitted to the CDC between 1 August and 23 September 2008. They were displaying symptoms common to chikungunya fever, such as fever, rash, muscle pain and joint swelling. Laboratory tests confirmed that all patients were indeed carrying the chikungunya virus. The majority of patients recovered completely within a week. Four patients, however, experienced persistent joint swelling; three in their fingers and one in their knees and shoulders.
The researchers found that patients with high viral load had unusually low numbers of lymphocytes and monocytes, but high numbers of neutrophils and C-reactive proteins in the blood—all signs of inflammation. During the acute phase of infection, patients with a high viral load also displayed abnormally high levels of pro-inflammatory cytokines—particularly interferon-α and interleukin–6.
When the disease reached the chronic phase, the researchers detected interleukin-17—a pro-inflammatory cytokine with important roles in bone tissue inflammation and destruction—in the blood. However, they found that only patients with persistent arthralgia had high levels of interleukin-6 and granulocyte-macrophage colony-stimulating factor, whereas patients who recovered completely had high levels of anti-inflammatory cytokine eotaxin.
Altogether, the results demonstrate that the viral load at the acute phase may determine specific patterns of pro-inflammatory cytokines and disease severity. At the chronic phase, however, the levels of interleukin-6 and granulocyte macrophage colony-stimulating factor determine the presence of persistent arthralgia.
The A*STAR-affiliated researchers contributing to this research are from the Singapore Immunology Network.