Neutrophil-mediated cartilage injury in vitro is enhanced by tumour necrosis factor alpha

1990 ◽  
Vol 10 (2) ◽  
pp. 85-90 ◽  
Author(s):  
I. C. Kowanko ◽  
E. J. Bates ◽  
A. Ferrante
Keyword(s):  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Tumour Necrosis Factor Alpha ◽  
Cartilage Injury ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Necrosis Factor

scholarly journals The neutrophil migration induced by tumour necrosis factor alpha in mice is unaffected by glucocorticoids

1997 ◽  
Vol 6 (1) ◽  
pp. 46-52 ◽  
Author(s):  
C. A. Cecilio ◽  
E. H. Costa ◽  
P. Ucelli ◽  
C. A. A. Chaves ◽  
M. C. Toffoli ◽  
...  
Keyword(s):  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Neutrophil Migration ◽  
Intraperitoneal Administration ◽  
Tumour Necrosis Factor Alpha ◽  
Necrosis Factor Alpha ◽  
Polyclonal Igg ◽  
Factor Alpha ◽  
Necrosis Factor

Macrophages harvested from the peritoneal cavities of rats release a neutrophil chemotactic factor (MNCF) in response to stimulation with Gram-negative bacterial lipopolysaccharide (LPS). MNCF has been shown to be active in rats treated with dexamethasone, a glucocorticoid that usually inhibits the neutrophil migration induced in this species by interleukin (IL)-1, tumour necrosis factor alpha (TNFα), IL-8, C5a and leukotriene B4(LTB4). Here we report that macrophages harvested from peritoneal cavities of mice, and stimulatedin vitrowith LPS, also release a factor that induces neutrophil migration in dexamethasone-treated animals. This chemotactic activity was neutralized by the incubation of the LPS-stimulated macrophage supernatants with a purified polyclonal IgG anti-mouse TNFα. In addition, significant amounts of TNF were detected in the supernatants. The neutrophil migration induced by intraperitoneal administration of recombinant murine TNFα was also unaffected by pretreatment of the mice with dexamethasone. Moreover, neutrophil migration induced by intraperitoneal injection of LPS was completely blocked by pretreatment of the mice with a monoclonal antibody against murine TNFα. In conclusion, our results support the hypothesis that, in contrast to the role of TNF in rats (where it indirectly induces neutrophil migration), in mice, it may be an important mediator in the recruitment of neutrophils to inflammatory sites.

Tumour necrosis factor alpha blockade impairs dendritic cell survival and function in rheumatoid arthritis

2009 ◽  
Vol 69 (6) ◽  
pp. 1200-1207 ◽  
Author(s):  
Helen M Baldwin ◽  
Toshiko Ito-Ihara ◽  
John D Isaacs ◽  
Catharien M U Hilkens
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cell ◽  
Dendritic Cell ◽  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Tumour Necrosis Factor Alpha ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Necrosis Factor

ObjectivesTumour necrosis factor alpha (TNFα) blockade is an effective therapy for rheumatoid arthritis (RA). The immunomodulatory effects of TNFα antagonists are thought to contribute to their therapeutic action. This study investigated whether anti-TNFα therapeutics exerted their immunoregulatory effects through modulation of dendritic cell (DC) function.MethodsTwo complementary approaches were taken: in the first ‘in vitro’ approach monocyte-derived DC from healthy donors were matured with lipopolysaccharide and treated with TNFα antagonists in vitro for 48 h. In the second ‘ex vivo’ approach monocyte-derived DC were generated from RA patients before and 8–12 weeks into anti-TNFα treatment. DC were analysed for survival, phenotype, cytokine production and T-cell stimulatory capacity.ResultsTNFα blockade during DC maturation in vitro induced approximately 40% of DC to undergo apoptosis. Importantly, the surviving DC displayed a semimature phenotype with reduced levels of HLA-DR, CD80, CD83, CD86 and CCR7, and their production of IL-10 was enhanced compared with DC matured without TNFα antagonists. Furthermore, anti-TNFα-treated DC were poor stimulators of T-cell proliferation and polarised T-cell development towards a higher IL-10/lower IFNγ cytokine profile. Similarly, DC derived from RA patients after anti-TNFα treatment showed impaired upregulation of CD80 and CD86 upon lipopolysaccharide activation and displayed poor T-cell stimulatory activity.ConclusionsThe data show that TNFα blockade has profound effects on DC function with downstream, potentially immunoregulatory, effects on T cells. These data provide an interesting new insight into the potential mechanism by which anti-TNFα drugs contribute to the restoration of immunoregulation in RA patients.

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