To review the concept of proinflammatory cytokines.
Review of published literature.
Academic (university hospital).
Cytokines are regulators of host responses to infection, immune responses, inflammation,
and trauma. Some cytokines act to make disease worse (proinflammatory), whereas others
serve to reduce inflammation and promote healing (anti-inflammatory). Attention also
has focused on blocking cytokines, which are harmful to the host, particularly during
overwhelming infection. Interleukin (IL)-1 and tumor necrosis factor (TNF) are proinflammatory
cytokines, and when they are administered to humans, they produce fever, inflammation,
tissue destruction, and, in some cases, shock and death. Reducing the biological activities
of IL-1 and TNF is accomplished by several different, but highly specific, strategies,
which involve neutralizing antibodies, soluble receptors, receptor antagonist, and
inhibitors of proteases that convert inactive precursors to active, mature molecules.
Blocking IL-1 or TNF has been highly successful in patients with rheumatoid arthritis,
inflammatory bowel disease, or graft-vs-host disease but distinctly has not been successful
in humans with sepsis. Agents such as TNF-neutralizing antibodies, soluble TNF receptors,
and IL-1 receptor antagonist have been infused into > 10,000 patients in double-blind,
placebo-controlled trials. Although there has been a highly consistent small increase
(2 to 3%) in 28-day survival rates with anticytokine therapy, the effect has not been
Anticytokine therapy should be able to "rescue" the patient whose condition continues
to deteriorate in the face of considerable support efforts. Unfortunately, it remains
difficult to identify those patients who would benefit from anticytokine therapy for