Decrease in IL-10 and increase in TNF-α levels in renal tissues during systemic inhibition of nitric oxide in...

Area of Science:

• Immunology
• Nephrology
• Biochemistry

Background:

• Nitric oxide synthase (NOS) inhibition via nitro-l-arginine methyl ester (l-NAME) increases proinflammatory tumor necrosis factor-alpha (TNF-α).
• The role of anti-inflammatory interleukin-10 (IL-10) in this process requires further elucidation.

Purpose of the Study:

• To investigate the hypothesis that nitric oxide (NO) inhibition suppresses interleukin-10 (IL-10) generation.
• To determine if suppressed IL-10 facilitates enhanced TNF-α production.

Main Methods:

• Measurement of IL-10 and TNF-α levels in plasma and renal tissues using ELISA and immunohistochemistry in mice.
• Administration of l-NAME to inhibit NOS, with or without a NO donor (SNAP) or IL-10 infusion.

Main Results:

• l-NAME treatment significantly decreased IL-10 levels and increased TNF-α levels in both plasma and renal tissues.
• Immunohistochemistry revealed downregulation of IL-10 and a 2.5-fold increase in TNF-α expression in renal cortical sections.
• Coinfusion with a NO donor or IL-10 infusion prevented or attenuated the l-NAME-induced changes.

Conclusions:

• NOS inhibition reduces endogenous IL-10 generation in the kidney.
• This reduction in IL-10 diminishes its immune-downregulating effect on TNF-α production, promoting inflammation.