Effect of L-arginine on intestinal water and sodium absorption Reply

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Phospholipase A 2 in inflammatory bowel disease EDITOR,-Increased release of proinflammatory eicosanoids such as prostaglandin E 2 and thromboxane B 2 from mononuclear cells occurs during relapse in patients with inflammatory bowel disease (IBD). 1 The key enzyme in eicosanoid synthesis is phospholipase A 2 (PLA 2 ).Raised serum concentrations of the PLA 2 group II isoenzyme can be detected by immunoassay during the acute stages of IBD. 2 We read with interest the recent article by Peterson et al about the role of a phospholipase A 2 activating protein, PLAP (Gut 1996; 39: 698-704).The authors showed clearly that PLAP can be detected in monocytes and granulocytes originating from intestinal mucosa of patients with Crohn's disease and ulcerative colitis.In addition to this finding, extracellular deposits of PLAP antigen were associated with blood vessels and oedematous fluid from the inflamed tissue.Peterson et al postulated that PLAP may be involved in increasing PLA 2 activity with consecutive eicosanoid generation in IBD.We propose a further possible mechanism of PLA 2 activation during acute IBD in which the pro-inflammatory cytokine interleukin-6 (IL-6) is a key mediator.Peripheral blood concentrations of this cytokine are raised during acute IBD. 3 We showed recently that recombinant human IL-6 alone can increase serum concentrations of PLA 2 group II isoenzyme in humans. 4 Therefore, we suggest that increased IL-6 concentrations during relapse of IBD are also able to induce PLA 2 by a diVerent mechanism from PLA 2 activation via PLAP.The important role of cytokines in the induction of PLA 2 was confirmed by Crowl et al, 5 who showed that IL-6 could induce PLA 2 in vitro.The molecular mechanism of this induction was further elucidated by detection of an IL-6 response element in the promoter region of the PLA 2 gene. 5 In conclusion, activation of PLA 2 by PLAP could be a possible mechanism for increased eicosanoid synthesis in IBD but direct induction of PLA 2 gene transcription by pro-inflammatory cytokines should be taken into account.Therefore, we suggest a study with parallel measurements of IL-6 and PLA 2 serum concentrations during acute relapse of IBD to correlate these parameters and to determine the profiles of occurrence of these inflammation markers.We have developed a radiometric assay which may be useful as a sensitive and reliable method for absolute measurements of the true PLA 2 group II enzyme activity in serum. 6 Parallel measurements using a PLA 2 group II immunoassay may also indicate whether activation or inhibitory factors of PLA 2 are also present in peripheral blood.

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