leukotriene-b4 and Convalescence

The role of LTB4 in Kawasaki disease as a chemo-attractant and immunomodulator is reviewed through our own experience and reports by other investigators. In our experiment using 19 patients, we measured calcium ionophore-stimulated LTB4 synthesis in PMNs obtained in three different stages of the illness (acute, convalescent and recovered phases). LTB4 synthesis was significantly increased in the convalescent phase of the illness. Other investigators showed increased serum-LTB4 concentration in acute as well as convalescent phases, suggesting that LTB4 participated in the inflammatory process of Kawasaki disease as an inflammatory mediator and immunomodulator. However, no difference was found in LTB4 synthetic activity in PMNs in any phases of the illness between the patients with and without coronary lesions, which indicated that LTB4 was not a parameter of coronary aneurysm formation. Therapeutic use of high-dose gamma-globulin showed a tendency to decreased LTB4 synthesis in PMNs, although it is not conclusive.

Topics: Child; Child, Preschool; Convalescence; Coronary Aneurysm; Female; Humans; Immunoglobulins, Intravenous; Infant; Leukotriene B4; Male; Mucocutaneous Lymph Node Syndrome; Neutrophils

Acute inflammation can be considered in terms of a series of checkpoints where each phase of cellular influx, persistence, and clearance is controlled by endogenous stop and go signals. It is becoming increasingly apparent that in addition to initiating the inflammatory response, eicosanoids may also mediate resolution. This suggests there are two phases of arachidonic acid release: one at onset for the generation of proinflammatory eicosanoids and one at resolution for the synthesis of proresolving eicosanoids. What is unclear is the identity of the phospholipase (PLA2) isoforms involved in this biphasic release of arachidonic acid. We show here that type VI iPLA2 drives the onset of acute pleurisy through the synthesis of PGE2, LTB4, PAF, and IL-1beta. However, during resolution there is a switch to a sequential induction of first sPLA2 (types IIa and V) that mediates the release of PAF and lipoxin A4, which, in turn, are responsible for the subsequent induction of type IV cPLA2 that mediates the release of arachidonic acid for the synthesis of proresolving prostaglandins. This study is the first of its kind to address the respective roles of PLA2 isoforms in acute resolving inflammation and to identify type VI iPLA2 as a potentially selective target for the treatment of inflammatory diseases.

Topics: Acute Disease; Animals; Arachidonic Acid; Carrageenan; Cells, Cultured; Convalescence; Corticosterone; Cyclooxygenase 2; Disease Progression; Enzyme Induction; Epithelial Cells; Fibroblasts; Group II Phospholipases A2; Group IV Phospholipases A2; Group V Phospholipases A2; Group VI Phospholipases A2; Interleukin-1; Isoenzymes; Leukotriene B4; Lipoxins; Macrophages; Male; Phospholipases A; Phospholipases A2; Platelet Activating Factor; Pleurisy; Prostaglandin-Endoperoxide Synthases; Rats; Rats, Wistar