|
本研究目的是探討葡萄球菌腸毒素A (staphylococcal enterotoxin A, SEA)
的致熱作用。靜脈注射SEA (10-100 ng/kg) 或血管脈叢終端器官
(organum vasculosum laminae terminalis, OVLT)注射SEA
(0.012-1.2 ng/kg)，可使兔子產生劑量相關性的發燒反應，而且和靜脈注射SEA
所引起的發燒比較，OVLT注射只需極少量的SEA就可引發相似的發燒現象。 靜脈注射
SEA，除了引起兔子體溫上升外，亦可同時誘導血清中干擾素 (interferon, IFN)、
腫瘤壞死因子 (tumor necrosis factor, TNF)、第二介白質
(interleukin-2,IL-2)的上升。靜脈注射SEA所引起的發燒反應及IFN、TNF、
IL-2的產生都可受anisomycin (蛋白質合成抑制劑，15 mg/kg，皮下注射) ，
indomethacin (環氧化酵素抑制劑，15 mg/kg，腹腔注射)，或 dexamethasone
(抗發炎免疫抑制劑，4 mg/kg，靜脈注射) 1小時前注射所抑制。連續4天靜脈注射
SEA，其所引起的發燒程度及IFN、TNF、IL-2的產生都較只接受一次靜脈注射SEA少。
1小時前OVLT投予anisomycin (50 ug/kg)， indomethacin (200 ug/kg)
或 diclofenac (環氧化酵素抑制劑，50 ug/kg)，dexamethasone (5 ug/kg)
或 aminoguanidine (誘導型一氧化氮合成酵素抑制劑，500 ug/kg) 都可抑制
靜脈或OVLT注射SEA所引起的發燒反應。OVLT注射anisomycin，dexamethasone
或 aminoguanidine亦會抑制靜脈注射SEA所產生的IFN、TNF及IL-2，而
indomethacin只會抑制IFN，對於TNF或IL-2則沒有顯著的抑制。SEA刺激人類週邊
血單核細胞 (peripheral blood mononuclear cells, PBMC) 的上清液，
靜脈注射到兔子體內，會引起劑量相關的發燒，而所引起的發燒反應在70 oC培養30分鐘
會被破壞。在抗體中和反應，以anti-human-IL-1*抗體中和上清液後，會減少上清液
的發燒反應。SEA加入anisomycin、dexamethasone 或 aminoguanidine，而和
PBMC一起培養，都可抑制SEA刺激PBMC所產生的亞硝酸鹽及細胞素，並且影響上清液的
發燒反應。綜合上述實驗結果顯示，SEA刺激PBMC所產生的細胞素，可媒介SEA的發燒
反應，而OVLT或血中單核細胞誘導型一氧化氮合成酵素、環氧化酵素-2及其他未知的
機制，可能和SEA引起發燒及產生細胞素有密切關係。
|
|
Intravenous (i.v., 10-100 ng/kg) or direct administration of
staphylococcal enterotoxin A (SEA) into the organum vasculosum
laminae terminalis (OVLT, 0.012-1.2 ng/kg) caused a
dose-dependent fever in rabbits. Compared with the fever induced
by i.v. injection, the OVLT route of injection required a much
lower dose of SEA to produce a similar fever. In parallel with
temperature change, the serum levels of interferon (IFN), tumor
necrosis factor (TNF) and interleukin-2 (IL-2) were elevated following systemic injection of SEA. Both the fever and the elevated levels of cytokines after SEA injection were attenuated by pretreatment with anisomycin (a protein synthesis inhibitor, 15 mg/kg, subcutaneously), indomethacin (a cyclooxygenase, COX, inhibitor, 15 mg/kg, intraperitoneally) or dexamethasone (an anti-inflammatory and immunosuppressive agent, 4 mg/kg, i.v.) in rabbits. Compared with rabbits that received a single injection of SEA, rabbits that received 4 consecutive injections of SEA produced a lesser increase in both the fever and the augmented cytokine production. Intra-OVLT pretreatment with anisomycin (50 mg/kg), indomethacin (200 mg/kg), diclofenac (a COX inhibitor, 50 mg/kg), dexamethasone (5 mg/kg) or aminoguanidine (a inducible nitric oxide synthase, iNOS, inhibitor, 500 mg/kg) inhibited the fever induced by i.v. or intra-OVLT injection of SEA. Intra-OVLT administration of anisomycin, dexamethasone or aminoguanidine inhibited the augmented IFN, TNF, and IL-2 production after i.v. injection
of SEA, while intra-OVLT injection of indomethacin only inhibited
the augmented IFN production. Intravenous injection of the supernatants from
SEA-stimulated peripheral blood mononuclear cells (PBMC) caused
a dose-related fever in rabbits. The supernatants after heating
at 70 oC for 30 min caused a decreased fever as compared to
those of the unheating supernatants. The fever induced by
SEA-stimulated supernatants was attenuated by administration of
neutralizing anti-human IL-1 b monoclonal antibody. Both
nitrite and pyrogenic cytokine production and fever were
suppressed by coincubation of SEA-stimulated PBMC with
anisomycin, dexamethasone or aminoguanidine. The data suggest
that the cytokines production released from the SEA-stimulated
PBMC mediates the SEA fever. The iNOS , COX-2 and other unknown
mechanisms located in OVLT and/or blood mononuclear cells are
related to the fever and the augmented cytokine production in
blood following exposure to SEA.
|
