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The biological response to planned and unplanned injuries is discussed in terms of the time course and both local and systemic states. In the systemic and local inflammatory response syndrome, the excess systemic cytokine reaction must be controlled. However, in the local inflammation-induced systemic immunosuppression syndrome, the fundamental defensive response should be maintained or even reinforced. Uniform measures for cytokine reaction are inadequate.

The priming effects of obstructive jaundice by bile duct ligation on interleukin (IL)-18-induced hepatic injury are investigated. The production of IL-12 and tumor necrosis factor-alpha increased 3 days after bile duct ligation. Subsequent IL-18 injection to rats with obstructive jaundice caused by BDL resulted in prominent interferon-gamma production and hepatic injury. These results suggest that IL-18 with IL-12 and/or tumor necrosis factor-alpha have synergistic effects on the induction of hepatic injury via interferon-gamma production on this model.

Aims: Group II phospholipase A[sub 2] (PLA[sub 2] ) is thought to play an important role in inflammation and tissue injury. It has been suggested that the inflammatory process is important in the setting and progression of myocardial ischemia or reperfusion. We measured plasma PLA[sub 2] as well as inflammatory cytokines in patients in the acute stage of myocardial infarction. Methods and Results: In 48 patients with acute myocardial infarction, blood samples were taken to measure plasma PLA[sub 2] , tumor necrosis factor-alpha (TNF-α) and interleukin-1β (IL-1β) 36–48 h after onset. Serial changes in plasma PLA[sub 2] were also examined in 15 consecutive patients in this group. Plasma PLA[sub 2] levels were significantly higher in complicated patients (Killip’s class ≥ II) than in uncomplicated patients (Killip’s class = I) (35.9 ± 11.9 vs. 5.3 ± 1.1 ng/ml, p < 0.01). Plasma PLA[sub 2] concentrations increased gradually over time during the first 3 days and at 36–48 h after onset were correlated with left-ventricular ejection fraction on admission (r = –0.42, p < 0.01), and with plasma TNF-α (r = 0.39, p < 0.01), but not with IL-1β. Conclusion: Plasma PLA[sub 2] concentrations rose during the acute stage of myocardial infarction, especially in severe cases mainly with heart failure. TNF-α may be associated with PLA[sub 2 ] activity as a potent stimulator in vivo. [ABSTRACT FROM AUTHOR]

It has been reported that a large number of carcinoma cells are able to produce a variety of cytokines. We also reported that many carcinoma cell lines constitutively produce IL-8 in supernatant cultures. To evaluate the in vivo function of IL-8 of carcinoma cells, we investigated the expression of IL-8 and IL-8 receptors (IL-8R) in human carcinoma cells and the role of IL-8 and IL-8R in the growth of carcinoma cells. IL-8 mRNA was detected in 16 out of 20 (80%) carcinoma cell lines and 20 out of 24 (83.3%) carcinoma tissues by Northern blot analysis. IL-8R mRNA was expressed in 7 out of 11 (63.6%) carcinoma cell lines by reverse transcriptase–polymerase chain reaction (RT-PCR). Neutrophil chemotactic activity in supernatant cultures of carcinoma cell lines correlated with immunoreactive IL-8 concentration. Growth of carcinoma cells was significantly inhibited in the presence of anti-IL-8 antibodies or IL-8R antisense oligonucleotides. These results revealed that IL-8 and IL-8R are expressed in the majority of carcinoma cells, and it suggests that they might play a role in the growth of carcinoma cells.On the other hand, the NF-κB/Rel families are crucial transcriptional factors for regulation of IL-8 in immune and inflammatory responses. To determine if IL-8 production in carcinoma cells is associated with activation of nuclear factor κB (NF-κB), we investigated MCF-7 breast carcinoma cells with 12-O-teradecanoyl-phorbol-13-acetate (TPA) treatment. After TPA treatment, ELISA showed IL-8 production was increasing in culture supernatant. Western blotting revealed that in concert with the decline in cytosolic IκB, NF-κB exhibited similar kinetics of translocation to the nucleus. Electrophoric mobility shift assay (EMSA) also revealed that activation of NF-κB. These findings suggest that activation of NF-κB regulates IL-8 expression in carcinoma cells. [Copyright &y& Elsevier]

Background: Interleukin-18 (IL-18) production is the main mechanism of hepatic injury in several animal models via further gamma interferon (IFN-γ) release. IL-18 also functions as an inducer of proinflammatory cytokines as TNF-α, which are also shown to induce organ injuries in many severe inflammatory conditions. To clarify the mechanism of hepatic injury developed in acute pancreatitis, plasma concentrations of IL-18 and its related cytokines were analyzed. Patients and methods: Plasma levels of IL-18, IL-12, IFN-γ, TNF-α, soluble TNF receptor (sTNF-R) and soluble Fas ligand (sFas-L) were measured by ELISA. Results: Plasma concentrations of IL-18 in patients with hepatic injury increased during the first few days apparently and remained so to some extent thereafter. However, IFN-γ showed no apparent increase in plasma concentrations. Those of TNF-α and sTNF-R remained increased in the hepatic injury group. Conclusion: These results suggest that IL-18 may act as a pro-inflammatory cytokine, which provokes the cytokine storm and eventually hepatic injury. [Copyright &y& Elsevier]

Objectives: We clarified a distinctive feature of response to surgical stress in elderly patients compared to nonelderly patients. Subjects: Two hundred and ninety-two consecutive patients received elective gastrointestinal surgery. Patients were analyzed for physiological status, cytokine levels, surgical stress parameters and postoperative status of SIRS and complications. Cytokine responses according to patient''s age: Plasma levels of interleukin 6 (IL-6) fluctuated in higher concentrations in elderly patients. Peak plasma levels of IL-6 were significantly high in patients aged over 75 years in total gastrectomy, over 65 years in pancreaticoduodenectomy and over 60 years in major hepatectomy. Mechanisms of hypercytokinemia in elderly patients: Renal dysfunction caused hypercytokinemia in elderly patients. Hypercytokinemia and SIRS: SIRS was more frequently encountered and continued for a long time in elderly patients, giving us an early sign of postoperative complications. Conclusions: In order to prevent postoperative complications in elderly patients, we must shorten status of SIRS due to excessive hypercytokinemia. [Copyright &y& Elsevier]