Possible co-factors

There are other theories about factors that could cause or act as co-factors to the development of KS. One hypothesis suggests that KS develops because the immune system is over-activated, with elevated cytokine levels stimulating the growth of early KS cells, which can eventually become cancerous. Once these cells have arisen in one part of the body they may spread in the bloodstream until they lodge in other tissues to cause additional lesions.

One of the overactive substances that may cause the development of KS lesions is oncostatin M, a growth factor that is secreted by activated T-cells that stimulates angiogenesis. Infections such as HIV that activate T-cells may lead to an increase in levels of oncostatin M. KS cells also produce high levels of other angiogenic factors such as basic fibroblast growth factor and interleukin-1.

The presence of HIV itself may play a role in KS. Studies have shown that the HIV tat gene seems to cause the development of KS-like lesions in mice, and the Tat protein produced by this gene stimulates the growth of human KS cells in the test tube. Antibodies against Tat appeared to block the development of KS cells in the test tube. Other studies have shown that HIV-infected T-cells secrete a substance called vascular endothelial growth factor (VEGF) which may induce vascular leakage and facilitate the development of KS.

The human papillomavirus (HPV), associated with cervical and anal cancer, is no longer considered to be a co-factor in the development of KS. Similarly, early theories that KS might be caused by cytomegalovirus (CMV) have now been discounted.

There have also been suggestions that KS might be linked to the recreational drug amyl nitrate (poppers), since KS is an AIDS-defining symptom largely restricted to gay and bisexual men, the most frequent users of poppers. A number of studies found that gay and bisexual men who have used poppers are much more likely to have developed KS as an AIDS-defining illness than non-users, but other studies have shown no clear relationship. One current hypothesis is that poppers could stimulate angiogenesis by turning up the expression of VEGF and its receptors, as has been demonstrated in the mouse.1

Retrospective studies have found that people with KS have a significantly reduced chance of developing HIV-related dementia. Researchers are investigating the mechanism by which HHV-8 inhibits HIV infection of the microglial cells in the brain.

References

  1. Tran DC et al. Inhalant nitrite exposure alters mouse hepatic angiogenic gene expression. Biochem Biophys Res Commun 310: 439-445, 2003