scholarly journals Detection of interleukin 8 and tumor necrosis factor in normal humans after intravenous endotoxin: the effect of antiinflammatory agents.

1991 ◽  
Vol 173 (4) ◽  
pp. 1021-1024 ◽  
Author(s):  
G D Martich ◽  
R L Danner ◽  
M Ceska ◽  
A F Suffredini
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Inflammatory Responses ◽  
Statistical Significance ◽  
Interleukin 8 ◽  
Necrosis Factor Alpha ◽  
Normal Humans ◽  
Necrosis Factor

Interleukin 8 (IL-8), a potent activator of neutrophils, may be important in the early host response to serious Gram-negative infections. IL-8 was measured with other acute phase cytokines (tumor necrosis factor alpha [TNF-alpha], IL-6 and IL-1 beta) in 25 normal humans randomized to receive either intravenous endotoxin alone or endotoxin after oral administration of ibuprofen or pentoxifylline, agents that alter some of the inflammatory responses induced by endotoxin in vitro. TNF immunoreactivity was maximum at 1.5 h, and total TNF (area under the curve) was 4.2- and 4.5-fold greater in subjects given endotoxin/ibuprofen compared to subjects given endotoxin alone (p = 0.026) or endotoxin/pentoxifylline (p = 0.004), respectively. IL-6 levels were maximum at 2-3 h and did not differ among the three groups. No IL-1 beta was detected in any subject. IL-8 levels peaked at 2 h in subjects given either endotoxin alone or endotoxin/pentoxifylline, falling towards baseline by 5 h. Subjects given endotoxin/ibuprofen had a more sustained rise in IL-8 with peak levels 2.8- and 2.5-fold higher at 3 h compared to endotoxin alone (p = 0.048) or endotoxin/pentoxifylline (p = 0.023), respectively. Differences in total IL-8 release among groups approached statistical significance (ANOVA, p = 0.07). This trend reflected the increased release of IL-8 by the subjects receiving ibuprofen compared to pentoxifylline (1.9-fold higher; p = 0.024). This suggests that cyclooxygenase products may provide important negative feedback loops for cytokine production in vivo. Increases in circulating IL-8 are part of the acute inflammatory response of humans to endotoxin. Altered cytokine responses caused by antiinflammatory therapy may have important implications for both host defense and injury during septicemia.

scholarly journals Abnormal lymphokine production: a novel feature of the genetic disease Fanconi anemia. II. In vitro and in vivo spontaneous overproduction of tumor necrosis factor alpha

Blood ◽  
1994 ◽  
Vol 83 (5) ◽  
pp. 1216-1225 ◽  
Author(s):  
F Rosselli ◽  
J Sanceau ◽  
E Gluckman ◽  
J Wietzerbin ◽  
E Moustacchi
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Fanconi Anemia ◽  
Tumor Necrosis ◽  
Tnf Alpha ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Necrosis Factor

Abstract We have previously shown an unbalanced cytokine production in Fanconi anemia (FA) cells, ie, an underproduction of interleukin 6 (IL-6) during growth. Among a number of cytokines analyzed, the only other anomalies detected concern tumor necrosis factor alpha (TNF alpha). In comparison to normal cells, this cytokine is overproduced by FA lymphoblasts from the four genetic complementation groups. Indeed, up to an eight-fold increase in TNF alpha is observed in the growth medium of FA cells. Moreover, addition of anti-TNF alpha antibodies partially corrects the FA hypersensitivity to treatment by mitomycin C (MMC). Treatment of FA cells with IL-6, which partially restored an almost normal sensitivity to MMC of FA cells also reduces the TNF alpha overproduction in FA lymphoblasts. No anomalies at the molecular level (Southern and Northern blot analyses) are detected for the TNF alpha gene and its mRNA. We have investigated the in vivo situation by assaying TNF alpha levels in the serum from FA homozygotes and obligate heterozygotes. In contrast to normal healthy donors or to aplastic anemia patients in whom serum TNF alpha is present only in trace amounts, all 36 FA patients and 21 FA parents monitored show a significantly (P < .001) higher level of serum TNF alpha activity. Consequently, abnormal TNF alpha production seems to be associated with the FA genetic background.

Somnogenic, pyrogenic, and anorectic activities of tumor necrosis factor-alpha and TNF-alpha fragments

1992 ◽  
Vol 263 (3) ◽  
pp. R708-R715 ◽  
Author(s):  
L. Kapas ◽  
L. Hong ◽  
A. B. Cady ◽  
M. R. Opp ◽  
A. E. Postlethwaite ◽  
...  
Keyword(s):  
Amino Acid ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Tnf Alpha ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Necrosis Factor

Exogenously administered tumor necrosis factor-alpha (TNF-alpha) elicits several symptoms of generalized infections such as fever, increased sleep, and anorexia. The aim of the present work was to localize these effects of TNF-alpha to specific amino acid sequences of the parent molecule by characterizing the in vivo and in vitro activities of several synthetic TNF-alpha fragments. Intracerebroventricular injection of TNF-alpha elicited dose-dependent fevers and increases in non-rapid-eye-movement sleep (NREMS) in rabbits. Four fragments also promoted NREMS and five elicited monophasic fevers. All of the somnogenic fragments share the amino acid sequence 31-36. In rats, TNF-alpha and one of the fragments [TNF-alpha-(69-100)] suppressed 12-h food intake. Furthermore, TNF-alpha increased the expression of the intercellular adhesion molecule-1 and enhanced interferon-gamma-induced HLA-DR expression in human glioblastoma cell line. In contrast, none of the fragments possessed these in vitro activities. Our in vivo results support the concept that there are biologically active regions in the TNF-alpha molecule.

scholarly journals Macrophage control of normal and leukemic erythropoiesis: identification of the macrophage-derived erythroid suppressing activity as interleukin-1 and the mediator of its in vivo action as tumor necrosis factor

Blood ◽  
1990 ◽  
Vol 75 (12) ◽  
pp. 2328-2334 ◽  
Author(s):  
P Furmanski ◽  
CS Johnson
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Interleukin 1 ◽  
Friend Virus ◽  
Erythroid Progenitors ◽  
Simultaneous Treatment ◽  
Necrosis Factor Alpha ◽  
Necrosis Factor

Abstract Macrophages have been shown to directly influence the growth and development of mature erythroid progenitors (CFU-E) in normal and erythroleukemic mice. We examined the mechanism by which macrophages mediate their effect on in vivo erythropoiesis. As reported for whole macrophages, serum-free supernatants (SN) from normal resident peritoneal macrophages suppressed in vivo normal and conventional Friend virus (CFV)-infected CFU-E and caused clinical regression of CFV- induced leukemia in mice. Macrophage SN had no effect on the erythropoietin (EPO)-independent CFU-E characteristic of infection with the polycythemia-inducing strain of Friend virus (FVP), or progression of FVP leukemia. Using biochemical, immunologic, and functional assays, the erythrosuppressive factor in macrophage SN was identified as interleukin-1 alpha (IL-1 alpha). The in vivo erythroid suppressive effects of macrophages, macrophage SN, and IL-1 alpha were reversed by simultaneous treatment with EPO. IL-1 alpha itself had no effect on CFU- E colony formation in vitro. Pretreatment of animals with antibodies to murine tumor necrosis factor-alpha (TNF-alpha) completely abrogated the suppression of CFU-E by macrophages, macrophage SN, or human recombinant IL-1 alpha. These results suggest that macrophages regulate erythropoiesis by production of IL-1 alpha, which in turn mediates its in vivo suppressive effects on CFU-E through TNF.

Sign in / Sign up

Export Citation Format

Share Document