Altered p38 mitogen-activated protein kinase expression in different leukocytes with increment of immunosuppressive mediators in patients with severe acute respiratory syndrome.
Severe acute respiratory syndrome (SARS) has spread to a global pandemic, especially in Asia. The transmission route of SARS has been clarified, but the immunopathogenesis of SARS is unclear. In an age-matched case-control design, we studied immune parameters in 15 SARS patients who were previously healthy. Plasma was harvested for detection of virus load, cytokines, and nitrite/nitrate levels, and blood leukocytes were subjected to flow cytometric analysis of intracellular mitogen-activated protein kinases (MAPKs) in different leukocytes. Patients with SARS had significantly higher IL-8 levels (p = 0.016) in early stage, and higher IL-2 levels (p = 0.039) in late stage than normal controls. Blood TNF-alpha, IL-6, and IL-10, and nitrite/nitrate levels were not significantly elevated. In contrast, TGF-beta and PGE(2) levels were significantly elevated in SARS patients. Five of the 15 SARS patients had detectable coronaviruses in blood, but patients with detectable and undetectable viremia had no different profiles of immune mediators. Flow cytometric analysis of MAPKs activation by phospho-p38 and phospho-p44/42 (extracellular signal-regulated kinase) expression showed that augmented p38 activation (p = 0.044) of CD14 monocytes associated with suppressed p38 activation (p = 0.033) of CD8 lymphocytes was found in SARS patients. These results suggest that regulation of TGF-beta and PGE(2) production and MAPKs activation in different leukocytes may be considered while developing therapeutics for the SARS treatment.
Lee
Chen-Hsiang
CH
Department of Internal Medicine, Chang Gung Memorial Hospital, 123 Ta-Pei Road, Niau-Sung, Kaohsiung 833, Taiwan.
Chen
Rong-Fu
RF
Liu
Jien-Wei
JW
Yeh
Wen-Tien
WT
Chang
Jen-Chieh
JC
Liu
Po-Mai
PM
Eng
Hock-Liew
HL
Lin
Meng-Chih
MC
Yang
Kuender D
KD
D000276:Adjuvants, Immunologic / Q000097:blood; D000328:Adult; D016022:Case-Control Studies; D017934:Coronavirus; D016207:Cytokines / Q000097:blood; D015232:Dinoprostone / Q000096:biosynthesis; D004196:Disease Outbreaks; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007962:Leukocytes / Q000201:enzymology* / Q000821:virology; D008875:Middle Aged; D020928:Mitogen-Activated Protein Kinases / Q000032:analysis / Q000096:biosynthesis*; D009566:Nitrates / Q000097:blood; D045169:Severe Acute Respiratory Syndrome / Q000097:blood / Q000209:etiology / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis; D019562:Viral Load; D048051:p38 Mitogen-Activated Protein Kinases
D000276:Adjuvants, Immunologic; D016207:Cytokines; D009566:Nitrates; D016212:Transforming Growth Factor beta; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D015232:Dinoprostone