Inflammation is mediated by a variety of soluble factors, including a group of secreted polypeptides known as cytokines. Inflammatory cytokines can be divided into two groups: those involved in acute inflammation and those responsible. Inflammation, the response of tissue to injury, is characterized in the acute phase by increased blood flow and vascular permeability along with the accumulation of fluid, leukocytes, and inflammatory mediators such as cytokines. Several cytokines play key roles in mediating acute inflammatory reactions, namely IL-1, TNF-a, IL-6, IL-11, IL-8 and other chemokines, G-CSF, and GM-CSF. The cytokines known to mediate chronic inflammatory processes can be divided into those participating in humoral inflammation, such as IL-3, IL-4, IL-5, IL-6, IL-7, IL-9, IL-10, IL-13, and transforming growth factor-b (TGF-b), and those contributing to cellular inflammation such as IL-1, IL-2, IL-3, IL-4, IL-7, IL-9, IL-10, IL-12, interferons (IFNs), IFN-g inducing factor (IGIF), TGF-b, and TNF-a and -b. Inflammatory abnormalities are a large group of disorders which underlie a vast variety of human diseases. Cytokines are regulators of host responses to infection, immune responses, inflammation, and trauma. Some cytokines act to make disease worse (proinflammatory cytokines), whereas others serve to reduce inflammation and promote healing (anti-inflammatory cytokines).
A proinflammatory cytokine is a cytokine which promotes systemic inflammation. Examples include IL-1 and TNF alpha. 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 statistically significant.
The anti-inflammatory cytokines are a series of immunoregulatory molecules that control the proinflammatory cytokine response. Cytokines act in concert with specific cytokine inhibitors and soluble cytokine receptors to regulate the human immune response. Their physiologic role in inflammation and pathologic role in systemic inflammatory states are increasingly recognized. Major anti-inflammatory cytokines include interleukin (IL)-1 receptor antagonist, IL-4, IL-6, IL-10, IL-11, and IL-13. Specific cytokine receptors for IL-1, tumor necrosis factor-alpha, and IL-18 also function as proinflammatory cytokine inhibitors.