ENHANCED TUMOR-NECROSIS-FACTOR IN ANTI-CD3 ANTIBODY STIMULATED DIABETIC NOD MICE - MODULATION BY PGE1 AND DIETARY-LIPID

被引：5

作者：

BAREL, D ^{[1
]}

BRENNAN, DC ^{[1
]}

JEVNIKAR, AM ^{[1
]}

BASTOS, M ^{[1
]}

STROM, TB ^{[1
]}

KELLEY, VR ^{[1
]}

机构：

[1] BRIGHAM & WOMENS HOSP,DEPT MED,IMMUNOGENET & TRANSPLANTAT LAB,75 FRANCIS ST,BOSTON,MA 02115

来源：

AUTOIMMUNITY | 1992年 / 13卷 / 02期

关键词：

AUTOIMMUNE DIABETES; TUMOR NECROSIS FACTOR; PROSTAGLANDIN-E1; NONOBESE DIABETIC MICE; FISH OIL;

D O I：

10.3109/08916939209001915

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Administration of OKT3 anti-CD3 monoclonal antibody (mAb) to patients for transplant rejection, is associated with a distinct and often severe clinical syndrome related to massive cytokine release. Previous reports have similarly demonstrated increased levels of serum tumor necrosis factor alpha (TNFalpha) in normal mice following administration of 1452-C11 anti-CD3 mAb. In this study, we compared serum TNFalpha levels at baseline and after anti-CD3 stimulation among three groups of mice: normal BALB/c controls, pre-diabetic non-obese diabetic (NOD) mice, and diabetic NOD mice. Baseline serum TNFalpha levels, as measured by L929 cell bioassay, were 2xhigher in diabetic NOD and 3xhigher in pre-diabetic NOD compared with BALB/c. Ninety minutes after anti-CD3 mAb stimulation, serum from BALB/c controls and pre-diabetic NOD contained 2- to 8-fold higher levels of TNF-alpha as compared to untreated control mice. In contrast, following anti-CD3 mAb, there was a dramatic 20-fold increase in serum TNFalpha in diabetic NOD mice (levels >5000 pg/ml). Additionally, anti-CD3 mAb increased the steady-state TNFalpha mRNA transcripts. Spleens from diabetic mice given anti-CD3 mAb had higher steady-state TNFalpha mRNA than spleen from normal mice similarly treated. The enhanced release of circulating TNFalpha after anti-CD3 mAb in diabetic NOD mice was abrogated by pre-treatment of mice with prostaglandin E1 (PGE1) 30 min prior to anti-CD3 mAb stimulation. Since dietary lipid can influence cytokine generation, serum from BALB/c mice fed fish (FO) or safflower oil (SO) supplemented diets was examined for TNFalpha before and after administration of anti-CD3 mAb. Mice supplemented with a FO diet had higher serum TNFalpha levels at baseline and following anti-CD3 mAB compared with mice fed SO. Supplementation of either lipid resulted in higher serum TNFalpha levels than mice fed standard laboratory chow (LC) (4.5% lipid). Taken together, we suggest the enhanced capacity of OKT3 to induce TNFalpha in patients with IDDM can be diminished by injection of PGE1. In addition, clearly the amount and composition of dietary lipid should be regulated in patients with IDDM receiving anti-CD3 mAb therapy.

引用

页码：141 / 149

页数：9

共 38 条

[1]

Cosimi A.B., Burton R.C., Colvin R.B., Goldstein G., Delmonico F.L., LaQuaglia M.P., Et al., Treatment of acute renal allograft rejection with OKT3 monoclonal antibody, Transplantation, 32, pp. 535-539, (1981)

[2]

Ferran C., Dy M., Merite S., Sheehan K., Schreiber R., Leboulenger F., Et al., Reduction of morbidity and cytokine release in anti-CD3 MoAb-treated mice by corticosteroids, Transplantation, 50, pp. 642-648, (1990)

[3]

Chatenoud L., Ferran Legendre C.C., Et al., Clinical use of OKT-3: The role of cytokine release and xenosensitization, J Autoimm, 1, pp. 631-640, (1988)

[4]

Ellenhorn J.D., Woodle E.S., Ghobreal I., Thistlewaite J.R., Blue-Stone J.A., Activation of human T cells in vivo following treatment of transplant recipients with OKT3, Transplantation, 50, pp. 608-612, (1990)

[5]

Abramowicz D., Schandene L., Goldman M., Crusiaux A., Vereerstraeten P., De Pauw L., Et al., Release of tumor necrosis factor, interleukin-2 and gamma-interferon after injection of OKT3 monoclonal antibody in kidney transplant recipients, Transplantation, 47, pp. 606-608, (1989)

[6]

Mackie J., Pankewycz O.G., Bastos M.B., Kelley V.E., Strom T.B., Dose related mechanisms of immunosuppression mediated by murine anti-CD3 antibody in pancreatic islets cell transplantation and delayed type hypersensitivity, Transplantation, 49, pp. 1150-1154, (1990)

[7]

Pankewycz O., Strom T.B., Rubin-Kelley V.E., Islet infiltrating T cell clones from non-obese diabetic mice that promote or prevent accelerated onset diabetes, Eur J Immunol

[8]

Haskins K., McDuffie M., Acceleration of diabetes in young NOD mice with a CD4 islet-specific T cell clone, Science, 249, pp. 1433-1436, (1990)

[9]

Shizuru J.A., Taylor-Edwards C., Banks B.A., Gregory A.K., Fathman C.G., Immunotherapy of the nonobese diabetic mouse: Treatment with an antibody to T helper lymphocytes, Science, 240, pp. 659-662, (1988)

[10]

Reich E.P., Sherwin R.S., Kanagawa O., Janeway C.A., An explanation for the protective effects of the MHC Class II I-E molecule in murine diabetes, Nature, 341, pp. 326-328, (1989)

← 1 2 3 4 →