Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cells of the macrophage lineage are considered to be of special importance in the defense of the host against tumor development and spread. Immunotherapeutic strategies to stimulate macrophage (MAC) tumor cytotoxicity make use of activating compounds such as gamma-interferon which are given systemically. However, there are several lines of evidence that in malignant disease the generation of cytotoxic effector MACs is impaired. Both defective cell maturation and loss of responsiveness to activation are described. Here, a first clinical phase I trial of adoptive immunotherapy in cancer patients using autologous MACs generated in vitro from blood monocytes (MOs) is reported. Mononuclear cells were isolated by cytapheresis and density centrifugation and cultured in hydrophobic Teflon bags for 7 days with 2% autologous serum and recombinant human gamma-interferon being present for the last 18 h. Cytotoxic MO-derived MACs were then purified by countercurrent elutriation and reinfused into the patient. A total of 72 therapies have been performed with patients being treated i.v. (n = 8) and i.p. (n = 7). In vitro generated MACs proved to be mature as judged by the expression of maturation-associated surface molecules (MAX antigens, CD16, CD51, CD71), were cytotoxic to U937 tumor cells, and were efficient secretory cells. Cell dose escalation was performed in the first patients beginning with 10(8) MACs to finally infuse the total number of cells recovered from one single cycle of isolation and culture. MAC yield varied from 1 to 17 x 10(8) representing 13-79% of MOs initially seeded. Adoptive MAc transfer was well tolerated. Side effects observed were low-grade fever (less than 38.5 degrees C), induction of the coagulation cascade, and abdominal discomfort after i.p. application. The procoagulant activity of MAC autografts was cell dose dependent and demonstrated by detection of circulating fibrin monomers and thrombin-antithrombin complexes. Biological responses observed included elevated serum neopterin levels and the appearance of interleukin-6 in sera and ascitic fluids. Indication of a possible therapeutic effect was only observed in i.p.-treated patients and consisted of disappearance of malignant ascites in 2 of 7 patients.
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PMID:Adoptive transfer of tumor cytotoxic macrophages generated in vitro from circulating blood monocytes: a new approach to cancer immunotherapy. 170 43

We have previously shown in rats that both intrathecal and systemic analgesia regimens attenuate surgery-induced increases in tumor susceptibility. The current study used indomethacin to assess the role of prostaglandins and inflammation-associated pain in mediating the deleterious effects of surgery on immunity and tumor susceptibility. Male and female Fischer 344 rats were anesthetized with halothane and were either subjected or not to experimental laparotomy, followed by the administration of indomethacin or vehicle. Tumor susceptibility was assessed by the lung retention assay using the syngeneic MADB106 mammary adenocarcinoma cell line, a natural killer (NK)-sensitive tumor that colonizes only in the lungs. Surgery resulted in a 2- to 3.5-fold increase in lung tumor retention, and indomethacin administration significantly reduced this effect in both sexes without affecting unoperated animals. Indomethacin also attenuated the reductions in rearing behavior evident after surgery, suggesting that it relieved abdominal discomfort. Surgery increased interleukin-6 levels and suppressed NK activity per milliliter blood. Indomethacin restored NK activity in both male and female rats but attenuated surgery-induced interleukin-6 increases only in the male rats. These findings further support our previous work implicating pain in mediating the tumor-enhancing effects of surgery and implicate prostaglandins in mediating this effect. If similar relationships occur in humans, controlling postoperative pain and inflammation must become a priority in the management of cancer patients undergoing surgery.
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PMID:Indomethacin attenuates the immunosuppressive and tumor-promoting effects of surgery. 1462 54