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Aberrant activation profile of cytokines and mitogen-activated protein kinases in type 2 diabetic patients with

C K Wong1, A W Y Ho, P C Y Tong

  • 1Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, China.

Clinical and Experimental Immunology
|April 12, 2007
PubMed

Insights

Type 2 diabetes involves inflammation. This study found higher levels of inflammatory cytokines and chemokines, and altered mitogen-activated protein kinase (MAPK) signaling in patients with type 2 diabetes, especially with nephropathy.

Area of Science:

  • Immunology
  • Endocrinology
  • Nephrology

Background:

  • Cytokine-induced inflammation plays a role in type 2 diabetes mellitus (DM) pathogenesis.
  • Diabetic nephropathy (DN) is a common complication associated with increased inflammation.

Purpose of the Study:

  • To investigate plasma cytokine/chemokine concentrations and ex vivo immune cell activation in type 2 DM patients with or without DN.
  • To explore the role of mitogen-activated protein kinases (MAPK) signaling in T helper (Th) cells and monocytes.

Main Methods:

  • Analyzed plasma cytokine/chemokine levels in 94 type 2 DM patients (with/without DN) and 20 controls.
  • Assessed ex vivo cytokine/chemokine production and MAPK phosphorylation (ERK, p38) in response to activation.
  • Correlated plasma markers with urine albumin-to-creatinine ratio in DN patients.

Main Results:

  • Significantly elevated plasma levels of TNF-alpha, IL-6, IL-18, CCL2, IL-10, CXCL8, CXCL9, CXCL10, and adiponectin in DN patients compared to controls and non-diabetic nephropathy (NDN) patients.
  • Increased ex vivo production of IL-6, CXCL8, CXCL10, CCL2, and CCL5 upon TNF-alpha activation in both NDN and DN patients.
  • Differential activation of MAPK pathways (ERK, p38) in Th cells and monocytes, particularly elevated in NDN and DN patients.

Conclusions:

  • Aberrant production of inflammatory cytokines and chemokines contributes to type 2 DM pathogenesis.
  • Differential activation of MAPK signaling in leukocytes is an underlying immunopathological mechanism in type 2 DM with DN.
  • These findings highlight key inflammatory pathways involved in diabetic complications.

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