Cytokine Responses In Patients Research Articles

Cytokine Responses in Patients with Pneumonia Caused by Chlamydia or Mycoplasma

The serum concentrations of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) were measured by enzyme immunoassays in 44 patients with Chlamydia (n = 13) or Mycoplasma (n = 14) pneumonia or influenza A infection (n = 17) and in 20 control subjects. The levels of IFN-γ were raised in 29/44 patients. The concentrations of IL-6 were raised in 32/44 patients. Raised levels of TNF-α were seen in 26/44 but there was no significant difference between the levels of the different groups of patients. All three cytokines indicated clinical recovery when acute and convalescent samples from 10 patients with Chlamydia pneumonia were analyzed. IFN-γ, IL6 and TNF-α are present in the circulation in the majority of patients with Chlamydia and Mycoplasma pneumonia and in influenza A infection. We suggest that repeated measurement of cytokines, such as IL-6, IFN-γ and TNF-α, may be useful in the management of lower respiratory tract infections but further studies are needed to define the value of cytokine measurements in acute pneumonia.

Human immunodeficiency virus infection alters antigen-induced cytokine responses in patients with active mycobacterial diseases.

Peripheral blood cells from 29 patients with active Mycobacterium avium (MAC) or Mycobacterium tuberculosis diseases were tested for mycobacterial antigen-induced interferon (IFN)-gamma and interleukin (IL)-4 production. Among MAC patients, human immunodeficiency virus (HIV) infection was associated with an 80% decrease in those who produced IFN-gamma, resulting in a predominantly type 2 cytokine profile. HIV infection in patients with tuberculosis correlates with a 37% increase in those producing IL-4 and a type 1 to type 0 profile shift. These qualitative changes were independent of CD4+ or CD8+ cell numbers. The amounts of both IFN-gamma and IL-4 were decreased in the HIV-infected population. Quantitative reduction of IFN-gamma was the result of fewer secreting cells rather than a down-regulation at the single-cell level. Disseminated disease was restricted to 2 of 5 HIV-infected MAC patients with a type 2 cytokine profile and 4 of 5 HIV-infected tuberculosis patients with a type 0 profile. These results demonstrated a shift in mycobacterial antigen-specific cytokine profiles from type 1 to type 0 and to type 2, in parallel with AIDS progression.

Peritoneal Cytokine Release after Elective Gastrointestinal Surgery and Postoperative Complications

Background: Laparotomy is known to give rise to systemic and local cytokine release. In the present study we investigated the course of the peritoneal response of tumor necrosis factor α (TNFα), interleukin (IL)-6, and IL-10 after elective gastrointestinal surgery and studied the differences in local cytokine response in patients developing postoperative complications. Methods: Twelve consecutive patients underwent pancreatoduodenectomy (n = 9) or biliary and gastric bypass (n = 3) for pancreatic carcinoma. Sampling (TNFα, IL-6, IL-10) of fluid from abdominal drains was performed at return to the recovery unit (T=0), and at 3, 6, 18, 30, 42, 54, 66, 78 hours. Systemic sampling was performed at T=0, 3, 6, 18, 42, 66 hours. Postoperative cytokine response in patients with and without postoperative complications was compared. Results: In patients without postoperative complications, peritoneal TNFα and IL-10 levels decreased in time ( P = 0.07 and P = 0.01, respectively), whereas IL-6 did not change significantly during sampling ( P = 0.28). Systemic IL-6 and IL-10 levels decreased 10-fold within 66 hours (IL-6, P = 0.04; IL-10, P = 0.06). Four patients experienced postoperative complications. All 4 patients with complications showed a second rise in peritoneal TNFα levels preceding the complication. All 4 patients had positive bacterial drain cultures from the abdominal drain, following the TNFα rise. Conclusions: After elective abdominal surgery, cytokines are released into the abdominal cavity. Intra-abdominal complications are accompanied or preceded by a peritoneal TNFα rise. In patients after elective gastrointestinal surgery, monitoring of peritoneal TNFα might be helpful in the early detection of severe intra-abdominal complications.

HBV-specific lymphoproliferative and cytokine responses in patients with chronic hepatitis B

Background/Aims: Hepatitis B virus specific T cell reponses are crucial for viral elimination but their nature is not fully understood. Methods: We studied the regulation of proliferation and cytokine production after antigenic stimulation in peripheral blood mononuclear cells from chronically HBV-infected patients and subjects with natural immunity after recovery from an acute infection. Proliferation and production of interferon-γ, IL-10 and tumor necrosis factor-α were determined after stimulation with HBcAg, HBeAg or HBsAg in the absence or presence of IL-12 or neutralizing antibodies to IL-12, interferon-γ, IL-4, IL-10 or tumor necrosis factor-α. Results: Upon stimulation with HBcAg or HBeAg, peripheral blood mononuclear cells from chronic hepatitis B virus patients displayed a clear class-II restricted proliferative response (SI greater than 2.5). Both interferon-γ (less than 50 IU/ml) and IL-10 levels up to 600 pg/ml were detected. Proliferative or cytokine responses to HBsAg were very weak or absent. Addition of IL-12 to HBeAg-stimulated cultures increased the production of interferon-γ to more than 200 IU/ml in all patients and slightly increased the production of IL-10. Neutralization of IL-10 increased the HBeAg-induced interferon-γ production but had no effect on tumor necrosis factor-α production. Addition of anti-IL-4 or anti-tumor necrosis factor-α had no significant influence on proliferation or cytokine release. Importantly, in both chronic hepatitis B virus patients and naturally immune subjects, IL-12 induced proliferative and interferon-γ responses in peripheral blood mononuclear cells stimulated with HBsAg. Conclusions: Our data indicate that peripheral blood mononuclear cells from chronic hepatitis B virus patients proliferate and produce interferon-γ and IL-10 upon HBeAg but not upon HBsAg stimulation. IL-12 augments the HBeAg-induced responses and, additionally, provokes proliferation and interferon-γ production in HBsAg-stimulated cultures.

The role of cytokines in cardiac surgery

Cytokines are a large and rapidly expanding group of polypeptides produced by many diferent cell types. Increasing interest has been focused on the role of cytokines as mediators of metabolic, immunological and endocrine responses to surgery. The cytokine response in patients undergoing cardiac surgery during cardiopulmonary bypass (CPB) is fairly well-defined and dominated by the proinflammatory cytokines IL-6, TNFα and IL-8 and the antiinflammatory cytokine IL-10. Little is known about the cytokine response in patients who develop postoperative complications but CPB with mechanical trauma and blood contact to artificial membranes is definitely an unphysiological state and may contribute to an uncontrollable response similar to that of patients with multiorgan failure and septic shock.