中脑导水管周围灰质内微量注射神经肽γ减弱慢性神经痛大鼠对伤害性刺激的反应

探讨神经肽Y(neuropeptide Y,NPY)在SD大鼠中脑导水管周围灰质(periaqueductal grey,PAG)对伤害性刺激反应的作用。应用热板和机械压力实验法,以大鼠后爪缩爪反应潜伏期(paw withdrawal latency,PWL)为痛阈指标。观察PAG内微量注射NPY对PWLS的影响。PAG内注射0．05、0．1、0．2nmol NPY均显著地增加慢性神经痛大鼠的双侧PWLS,且呈量效关系。NPY引起的PWLs增加可被Y1受体拮抗剂和阿片受体拮抗剂所阻断。结果提示,在大鼠PAG微量注射NPY可产生明显的镇痛作用。     

HO/CO在甲醛炎性痛大鼠脊髓痛传导及痛觉过敏产生中的作用

目的:探讨血红素氧合酶/一氧化碳(HO/CO)在甲醛诱导的大鼠自发痛和痛觉过敏形成中的作用。方法:采用鞘内注射的方法,在甲醛炎性痛大鼠和正常大鼠分别给予HO抑制剂Znpp和HO激动剂Hemin;采用加权积分法对痛反应进行评分以代表痛反应程度;采用观察热辐射缩足潜伏期和机械刺激缩足反射阈值表示热和机械性痛觉过敏的程度。结果:Znpp各剂量组与单纯甲醛组相比,大鼠痛反应评分明显降低,且Znpp剂量越大,对大鼠痛反应的抑制作用越明显;与单纯甲醛组相比,Znpp各剂量组大鼠注射足热辐射缩足潜伏期和机械刺激缩足反射阈值均无明显变化,而非注射足热辐射缩足潜伏期和机械刺激缩足反射阈值均明显升高,且Znpp的剂量越大,这种改变越明显。正常大鼠鞘内注射HO的激动剂Hemin后,双侧足热辐射缩足潜伏期和机械刺激缩足反射阈值均明显降低。结论:鞘内给予HO抑制剂可明显抑制甲醛诱导的自发痛反应及热和机械性痛觉过敏程度;正常大鼠鞘内给予HO激动剂可诱发热和机械性痛觉过敏的产生,提示HO/CO系统参与脊髓伤害性信息的传导和痛觉过敏的形成过程。     

脑室内或脑组织内微量注射吗啡的镇痛效应

(一)本文报告利用家兔脑室內注射和脑內微量注射方法,在保持中枢神經系統完整的条件下,研究嗎啡鎮痛作用部位的結果。 (二)脑室內注射20微克(相当于靜脉剂量的1/500—1/1000左右)可以产生明显而持久的鎮痛作用。注射后1—4分钟即表現作用。根据药液分布的范围等推測作用部位在第四脑室以上水平。 (三)脑室內注射嗎啡对光热刺激鼻部或后肢的痛反应都有效,对电刺激牙髓的痛反应也有效。脑室內注射多种其他药物不产生鎮痛作用。因此鎮痛是全身性的,而且是嗎啡特异作用的表現。 (四)脑內微量注射嗎啡以第三脑室周围灰貭作用最明显,10微克剂量即有鎮痛作用。側脑室壁的尾状核、透明隔以及皮貭下其他部位,注射較大剂量仍无鎮痛作用。 (五)本文提出第三脑室壁灰貭是嗎啡发揮鎮痛的作用部位的新的观点。     

中脑导水管周围灰质内微量注射神经肽Y减弱慢性神经痛大鼠对伤害性刺激的反应

探讨神经肽Y(neruopride Y, NPY) 在SD大鼠中脑导水管周围灰质 (periaqueductal grey, PAG) 对伤害性刺激反应的作用.应用热板和机械压力实验法,以大鼠后爪缩爪瓜潜伏期(paw withdrawal latency, PWL) 为痕阈指标, 观察PAG 内微量注射NPY对PWLs的影响.PAG内注射 0.05、0.1、 0.2 nmol NPY 均显著地增加慢性神经痛大鼠的双侧PWLs, 且呈量效关系.NPY引起的PWLs增加可被Y1受体拮抗剂和阿片剂所阻断.结果提示,在大鼠PAG 微量注射NPY可产生明显的镇痛作用.     

IL—1β,IL—lra对戊四氮致痫大鼠行为及皮层,海马脑电的 …

目的：了解白细胞介素１β（ＩＬ－１β）在癫痫发作中的作用。方法：采用记录脑图（ＥＥＧ）同时观察行为的方法,观察ＩＬ－１β和ＩＬ－１受体拮抗剂（ＩＬ－１ｒａ）测脑室注射对戊四氮（ＰＴＺ）致痫大鼠和皮层、海马ＥＥＧ的影响。结果：ＩＬ－１β能明显缩短ＰＴＺ致大鼠急性惊厥发作及痫波发放的潜伏期,增加痫波的发放频率。ＩＬ－１ｒａ能减少急性惊厥痫波放频率,对急性惊厥发主痫波发放的潜伏期和惊厥发作强度无明显影响     

脊髓水平给予胍丁胺对鞘内吗啡镇痛的影响

目的：观察脊髓水平给予胍丁胺对鞘内吗啡镇痛作用的影响。方法：30只sD大鼠随机分为3组（n=10）：C1组：鞘内注射生理盐水（10出）;M1组：鞘内注射吗啡（15μg／10μl）;AMI组：鞘内同时给予吗啡15μg＋胍丁胺12．5μg／10出。所有大鼠均于鞘内给药后5min于跖部皮下注射蜜蜂毒50m（0．2mg）致痛,观察并纪录1h内大鼠的自发缩足反射次数。另30只SD大鼠分组为C2,M2和AM2（n=10）,每组给药分别同前,用来测定机械痛阈和热刺激阈值。结果：与C1组比较,M1组1h内大鼠的自发缩足反射次数显著减少,提示鞘内注射吗啡对蜜蜂毒诱致的自发痛具有显著性抑制作用（P〈0．05）;鞘内同时给予吗啡和胍丁胺（AM1组）,大鼠自发缩足反射次数进一步减少,与M1组比较具有显著性意义（P〈0．05）。与对照组C2组比较,M2组大鼠的热刺激闽值和机械性痛闽明显提高;AM2组热刺激潜伏期显著延长,机械刺激阈值显著提高;AM2组与M2组比较热刺激潜伏期和机械刺激阈值有统计学差异（P〈0．05）。结论：鞘内胍丁胺和吗啡联合用药可显著增强吗啡对蜜蜂毒诱致自发痛的抑制作用,具有加强效应。     

阻断缰核或内侧前脑束对 L-谷氨酸刺激隔区引起的镇痛作用的影响

以辐射热-甩尾潜伏期作为测定大鼠痛阈的指标,用向隔区内微量注射 L-谷氨酸和向缰核或内侧前脑束微量注射利多卡因,可逆性刺激和阻断上述核团。L-谷氨酸刺激隔区使大鼠痛阈明显提高,并且在13.6—100nmol 呈现剂量-效应关系。利多卡因阻断缰核,使隔区的镇痛作用明显减弱(P<0.001)。而阻断内侧前脑束对隔区的镇痛作用无明显影响(P>0.05)。结果表明隔区在脊髓水平抑制痛觉信息的传导主要是下行通过缰核实现的。     

大鼠侧脑室注射精氨酸加压素对针刺镇痛的影响

以钾离子透入法引起大鼠甩尾反应为指标,测定动物的痛阈。由侧脑室注射精氮酸加压素(AVP)后,大鼠痛阈升高33.6％～68.5％,针刺镇痛效应明显加强,痛阈提高202.4％～302.7％。脑室注射抗精氨酸加压素血清,动物痛阈虽无明显变化,但针刺镇痛效应明显削弱,痛阈仅增加41.6％～71.0％。注射抗β-内啡肽血清和抗强啡肽A血清并不阻断AVP增强针刺镇痛效应。本工作的结果提示,脑内AVP参与针刺镇痛,这种作用与脑内内源性β-内啡肽和强啡肽的关系不甚密切。     

改良CCI 大鼠痛行为学检测与损伤区自发放电活动再观察

目的:应用改良CCI模型研究外周神经损伤后痛觉过敏和自发放电各自特征及相互关系.方法:雄性SD大鼠,随机分为CCI组和Sham组,分别于术前1天和术后1、4、7、9、11、14天测定机械刺激缩足反射阈值和热缩腿反射潜伏期,同时选取术侧机械刺激缩腿反射阈值低于4g或者术侧和健侧热缩腿反射潜伏期差异大于2s的CCI模型大鼠观察术后4-14天损伤区自发放电活动.结果:神经纤维损伤后,机械痛敏和热痛敏随时间表现为逐渐增强,同时在损伤区观察到三类放电模式:整数倍放电阵发放电和周期放电.结论:术后大鼠机械痛阈和热痛阈逐渐降低,机械痛敏的产生和损伤区自发放电活动关系密切,不同的放电模式可能代表不同的传入信息.     

改良CCI大鼠痛行为学检测与损伤区自发放电活动再观察

目的：应用改良CCI模型研究外周神经损伤后痛觉过敏和自发放电各自特征及相互关系。方法：雄性SD大鼠,随机分为CCI组和Sham组,分别于术前1天和术后1、4、7、9、11、14天测定机械刺激缩足反射阈值和热缩腿反射潜伏期,同时选取术侧机械刺激缩腿反射阈值低于4g或者术侧和健侧热缩腿反射潜伏期差异大于2s的CCI模型大鼠观察术后4-14天损伤区自发放电活动。结果：神经纤维损伤后,机械痛敏和热痛敏随时间表现为逐渐增强,同时在损伤区观察到三类放电模式：整数倍放电﹑阵发放电和周期放电。结论：术后大鼠机械痛阈和热痛阈逐渐降低,机械痛敏的产生和损伤区自发放电活动关系密切,不同的放电模式可能代表不同的传入信息。     

Increase of nociceptive threshold induced by intrathecal injection of interleukin-1beta in normal and carrageenan inflammatory rat

The present study was to investigate the effect of intrathecal (i.t.) injection of interleukin-1 beta (IL-1 beta) on nociception in normal and inflammatory rats. Peripheral inflammation was induced by intraplantar injection (i.pl.) of carrageenan into unilateral hind paw. The nociceptive threshold to noxious thermal stimulation was measured by the paw withdrawal latency (PWL). Intrathecal injection of IL-1 beta (10 ng, 100 ng) significantly increased PWL in normal rats, the peak occurred at 5 min and the effect lasted for 30 min. Similarly, IL-1 beta (10 ng, 100 ng, i.t.) significantly increased the PWL and lasted for more than 60 min in inflammatory rats. Both in normal and inflammatory rats, the IL-1 beta-induced antinociceptive effect was completely abolished by IL-1ra (50 ng, i.t.), and apparently attenuated by naloxone (10 microg, i.t.) or mianserin (20 microg, i.t.). These results suggest that IL-1 beta produces antinociceptive effect by binding IL-1 receptor at the spinal level, and is related to the activation of opioid and 5-HT systems.     

Interleukin-6 is a centrally acting endogenous pyrogen in the rat.

Intracerebroventricular (i.c.v.) injection of human recombinant interleukin-6 (IL-6; 20-100 ng) caused significant increases in colonic temperature and resting oxygen consumption (VO2) in conscious rats. These effects were prevented by pretreatment with a cyclooxygenase inhibitor (flurbiprofen, 1 mg/kg, i.p.) or a corticotrophin-releasing factor antagonist (alpha-helical CRF9-41, 25 micrograms, i.c.v.). Higher doses of IL-6 (i.c.v.) caused only small changes in VO2 and temperature, and very high doses given intravenously (i.v.) (4 micrograms/kg) were required to stimulate these parameters. Central injection of anti-rat IL-6 antibody inhibited the effects of interleukin-1 beta (i.c.v.) or endotoxin injection (i.p.) on colonic temperature and VO2 in conscious rats. These data indicate that IL-6 is an important endogenous pyrogen that acts within the central nervous system.     

Reperfusion-induced arrhythmias and lethality are reduced by a 2KDa heparin fragment

The influence of a low molecular weight heparin (Oligo-H, m.w. 2KDa) on ventricular arrhythmias and lethality induced by heart reperfusion following a 5 min coronary occlusion was studied in anesthetized rats. Both intravenous (i.v.) and subcutaneous (s.c.) injection of the compound doseand time-dependently prevented the reperfusion syndrome: in all salinepretreated animals post-ischemic reperfusion induced ventricular tachycardia (VT), which degenerated into ventricular fibrillation (VF) in 25 out of 30 rats, with a mortality rate of 73%; on the other hand, in rats I.V. Or s.c. pretreated with Oligo-H (20 mg/kg, 30 and 90 min, respectively, before coronary occlusion), VT occurred in 4 out of 10–11 animals and degenerated into VF in 2–3 out of 10–11 animals, with a mortality rate of 18–20%. Even more effective was a low molecular weight dermatan sulfate (Oligo-Ds, M.w. 2.1KDa). In rats treated with lidocaine, used as reference compound, at the dose of 5 mg/kg i.v. 10 min before coronary occlusion, VT occurred in 2 out of 10 animals and degenerated into VF in 1 out of 10 animals, with a mortality rate of 10%. It is concluded that low molecular weight glycosaminoglycans significantly reduce the consequences of heart reperfusion.     

Central injection of nicotine increases hepatic and splenic interleukin 6 (IL-6) mRNA expression and plasma IL-6 levels in mice: involvement of the peripheral sympathetic nervous system.

Accumulating evidence suggests that plasma levels of interleukin 6 (IL-6), a major cytokine stimulating the synthesis of acute-phase proteins, are intimately regulated by the central nervous system. Nicotine, one of the major drugs abused by humans, has been shown to affect immunological functions. In the present study, effects of intracerebroventricular (i.c.v.) injection of nicotine on plasma IL-6 levels were investigated in mice. Nicotine administered i.c.v. dose-dependently increased plasma IL-6 levels; the lowest effective dose was 0.3 ng/mouse and the maximal effect was attained with the dose of 105 ng/mouse. The nicotine (105 ng/mouse, i.c.v.)-induced plasma IL-6 levels peaked at 3 h and approached basal levels 6 h after injection. Mecamylamine, a nicotinic receptor antagonist, blocked nicotine-induced plasma IL-6 levels. Depletion of peripheral norepinephrine with 6-hydroxydopamine [100 mg/kg, intraperitoneal (i. p.)] inhibited the nicotine-induced plasma IL-6 levels by 57%, whereas central norepinephrine depletion with 6-hydroxydopamine (50 microgram/mouse, i.c.v.) had no effect. Pretreatment with prazosin (alpha1-adrenergic antagonist; 1 mg/kg, i.p.), yohimbine (alpha2-adrenergic antagonist; 1 mg/kg, i.p.), and ICI-118,551 (beta2-adrenergic antagonist; 2 mg/kg, i.p.), but not with betaxolol (beta1-adrenergic antagonist; 2 mg/kg, i.p.), inhibited nicotine-induced plasma IL-6 levels. Among the peripheral organs, including the pituitary, adrenals, heart, lung, liver, spleen, and lymph nodes, nicotine (105 ng/mouse, i.c.v.) increased IL-6 mRNA expression only in the liver and spleen, which was inhibited by peripheral norepinephrine depletion. These results suggest that stimulation of central nicotinic receptors induces plasma IL-6 levels and IL-6 mRNA expression in the liver and spleen via the peripheral sympathetic nervous system, alpha1-, alpha2-, and beta2-adrenoreceptors being involved.     

美普他酚及其同分异构体对角叉菜胶引起的炎症大鼠具有抗热痛敏作用

实验以清醒大鼠的缩腿潜伏期为指标,观察了腹腔注射美普他酚及其同分异构体112824和112825对角叉菜胶引起的热痛敏的影响.外周炎症由单侧足底注射角叉菜胶(2 mg/100 μl)引起.注射角叉菜胶3 h后,注射侧后肢局部红肿及热痛过敏反应达到高峰,持续数小时.腹腔注射0.1 mg/kg美普他酚对炎症和非炎症侧后肢的缩腿潜伏期无明显影响(P＞0.05,n=8).腹腔注射1mg/kg和10 mg/kg美普他酚对炎症和非炎症侧后肢产生明显的抗痛敏和抗伤害效应,且对炎症侧缩腿反应的抑制(抗痛敏)作用明显强于非炎症侧(抗伤害)(P＜0.05,n=8～11).预先腹腔注射1.5 mg/kg纳洛酮明显阻断美普他酚引起的抗伤害和抗痛敏效应.腹腔注射美普他酚的同分异构体112824(1 mg/kg)和112825(1.5 ms/kg)可产生与美普他酚类似的抗痛敏作用,该效应可被预先腹腔注射1.5 mg/kg纳洛酮完全阻断.提示美普他酚及其同分异构体具有明显抗伤害和抗痛敏作用,且以后者为强.该作用主要通过mu阿片受体介导.本研究为扩展美普他酚及其同分异构体在临床上的应用提供了依据.     

Induction of nociceptive responses by intrathecal injection of interleukin-1 in mice.

Intrathecal (i.t.) injection (between lumbar vertebrae 5 and 6) into mice of a markedly low dose of IL-1alpha (3x10(-4) fmol or 5.4 fg in 5 microl per mouse) induced behaviors involving scratching, biting, and licking of non-stimulated hindpaws. The IL-1-induced behaviors appeared within 10 min of the injection of IL-1alpha, peaked at 20-40 min, and had disappeared 60 min after the injection. The IL-1-induced behaviors were similar to the nociceptive responses induced in mice by i.t. injection of substance P (SP) or subcutaneous (s.c.) injection of formalin into the footpad. The IL-1-induced behaviors were suppressed by intraperitoneal morphine, indicating that they are nociceptive responses. The nociceptive responses induced by 3x10(-4) (5.4 fg) of IL-1alpha were almost completely suppressed by co-injection of 0.3 fmol (7.2 pg) of an IL-1 receptor antagonist (IL-1ra). An antiserum against substance P, but not an antiserum against somatostatin, suppressed the IL-1-induced nociceptive responses. The nociceptive responses induced by s.c. injection of 2% formalin into the footpad were also inhibited by i.t. injection of 30 pmol (720 ng) of IL-1ra. These results suggest that IL-1 may play a role in hyperalgesia in mice by acting as a factor augmenting pain transmission in the spinal cord at least in part by either directly or indirectly releasing substance P.     

Vagus-mediated activation of mucosal mast cells in the stomach: effect of ketotifen on gastric mucosal lesion formation and acid secretion induced by a high dose of intracisternal TRH analogue.

TRH analogue, RX 77368, injected intracisternally (i.c.) at high dose (3 microg/rat) produces gastric mucosal lesion formation through vagal-dependent pathway. The gastric mucosal hyperemia induced by i.c. RX 77368 was shown to be mediated by muscarinic vagal efferent fibres and mast cells. Furthermore, electrical vagal stimulation was observed to induce gastric mucosal mast cell degranulation. The aim of the study was to assess the influence of ketotifen, a mast cell stabilizer, on RX 77368-induced gastric lesion formation and gastric acid secretion. RX 77368 (3 microg, i.c.) or vehicle (10 microL, i.c.) was delivered 240 min prior to the sacrifice of the animals. Ketotifen or vehicle (0.9% NaCl, 0.5 mL) was injected intraperitoneally (i.p.) at a dose of 10 mg x kg(-1) 30 min before RX 77368 injection. The extent of mucosal damage was planimetrically measured by a video image analyzer (ASK Ltd., Budapest) device. In the gastric acid secretion studies, the rats were pretreated with ketotifen (10 mg x kg(-1), i.p.) or vehicle (0.9% NaCl, 0.5 mL, i.p.), 30 min later pylorus-ligation was performed and RX 77368 (3 microg, i.c.) or vehicle (0.9% NaCl, 10 microL, i.c.) was injected. The rats were killed 240 min after i.c. injection, and the gastric acid secretion was measured through the titration of gastric contents with 0.1 N NaOH to pH 7.0. RX 77368 (3 microg, i.c.) resulted in a gastric mucosal lesion formation involving 8.2% of the corpus mucosa (n = 7). Ketotifen elicited an 85% inhibition on the development of mucosal lesions (n = 7, P < 0.001) whereas ketotifen alone had no effect on the lesion formation in the mucosa (n = 7). The RX 77368 induced increase of gastric acid secretion was not influenced by ketotifen pretreatment in 4-h pylorus-ligated animals. Central vagal activation induced mucosal lesion formation is mediated by the activation of mucosal mast cells in the stomach. Mast cell inhibition by ketotifen does not influence gastric acid secretion induced by i.c. TRH analogue in 4-h pylorus-ligated rats.     

CCK-8对内毒素休克大鼠肺脏细胞因子的抑制效应

观察八肽胆囊收缩素(cholecystokinin-octapeptide,CCK-8）改善脂多糖(lipopolysaccharide,LPS）引起的大鼠内毒素性休克（endotoxic shock,ES）过程中血清及肺脏细胞因子的变化,探讨p38比裂素活化蛋白激酶（p38 mito-gen-activated protein kinase,p38 MAPK）的信号转导作用。用生理多道记录仪观察尾静脉注入LPS(p38 mito-gen-activated protein kinase,p38 MAPK）的信号转导作用。用生理多道记录仪观察尾静脉注入 LPS（8mg/kg i.v.）复制的SD大鼠ES模型、LPS注入前10min尾静脉注入CCK-8(40ug/kg i.v.）、单独注入CCK-8(40Uug/kg i.v.）或生理盐水（对照）的四组大鼠平均动脉血压（MAP）的改变,应用ELISA试剂盒检测血清和肺脏中炎性细胞因子（TNF-a、IL-1β和IL-6）的变化。用Western blot检测肺脏p38 MAPK的表达。结果显示：CCK-8可改善LPS引起的大鼠MAP的下降。与对照组相比,LPS可显著增加血清和肺脏TNF-a、IL-1β和IL-6含量;CCK-8可显著抑制LPS诱导的血清和肺脏TNF-a、IL-1β和IL-6的增加。CCK-8可增加ES大鼠肺脏磷酸化p38 MAPK的表达。结果提示CCK-8可改善ES大鼠MAP的降低,并对肺脏促炎性细胞因子过量产生有抑制作用,p38MAPK可能参与了其信号转导机制。     

Effects of vagotomy on serum endotoxin, cytokines, and corticosterone after intraperitoneal lipopolysaccharide

The vagus nerve appears to play a role in communicating cytokine signals to the central nervous system, but the exact extent of its involvement in cytokine-to-brain communication remains controversial. Recently, subdiaphragmatic vagotomy was shown to increase bacterial translocation across the gut barrier and thus may cause endotoxin tolerance. The current experiment tested whether or not vagotomized animals have similar systemic responses to endotoxin challenge as do sham-operated animals. Subdiaphragmatically vagotomized and sham-operated animals were injected intraperitoneally with one of three doses (10, 50, 100 microg/kg) of lipopolysaccharide (LPS) or vehicle, and blood samples were taken at 15, 30, 60, 90, and 120 min after the injection. The intraperitoneal injection of LPS increased circulating LPS levels at all time points examined. In addition, all three doses of LPS significantly increased serum interleukin (IL)-1beta, IL-6, and corticosterone in both control and vagotomized rats. In conclusion, vagotomy itself has no marked effect on circulating endotoxin levels or the production of IL-1beta, IL-6, or corticosterone in blood after an intraperitoneal injection of LPS.     

Kupffer cell-generated PGE2 triggers the febrile response of guinea pigs to intravenously injected LPS

Because the onset of fever induced by intravenously (i.v.) injected bacterial endotoxic lipopolysaccharides (LPS) precedes the appearance in the bloodstream of pyrogenic cytokines, the presumptive peripheral triggers of the febrile response, we have postulated previously that, in their stead, PGE2 could be the peripheral fever trigger because it appears in blood coincidentally with the initial body core temperature (Tc) rise. To test this hypothesis, we injected Salmonella enteritidis LPS (2 microg/kg body wt i.v.) into conscious guinea pigs and measured their plasma levels of LPS, PGE2, TNF-alpha, IL-1beta, and IL-6 before and 15, 30, 60, 90, and 120 min after LPS administration; Tc was monitored continuously. The animals were untreated or Kupffer cell (KC) depleted; the essential involvement of KCs in LPS fever was shown previously. LPS very promptly (<10 min) induced a rise of Tc that was temporally correlated with the elevation of plasma PGE2. KC depletion prevented the Tc and plasma PGE2 rises and slowed the clearance of LPS from the blood. TNF-alpha was not detectable in plasma until 30 min and in IL-1beta and IL-6 until 60 min after LPS injection. KC depletion did not alter the times of appearance or magnitudes of rises of these cytokines, except TNF-alpha, the maximal level of which was increased approximately twofold in the KC-depleted animals. In a follow-up experiment, PGE2 antiserum administered i.v. 10 min before LPS significantly attenuated the febrile response to LPS. Together, these results support the view that, in guinea pigs, PGE2 rather than pyrogenic cytokines is generated by KCs in immediate response to i.v. LPS and triggers the febrile response.