An Intense and Short-Lasting Burst of Neutrophil Activation Differentiates Early Acute Myocardial Infarction from Systemic Inflammatory Syndromes

BACKGROUND: Neutrophils are involved in thrombus formation. We investigated whether specific features of neutrophil activation characterize patients with acute coronary syndromes (ACS) compared to stable angina and to systemic inflammatory diseases. METHODS AND FINDINGS: The myeloperoxidase (MPO) content of circulating neutrophils was determined by flow cytometry in 330 subjects: 69 consecutive patients with acute coronary syndromes (ACS), 69 with chronic stable angina (CSA), 50 with inflammation due to either non-infectious (acute bone fracture), infectious (sepsis) or autoimmune diseases (small and large vessel systemic vasculitis, rheumatoid arthritis). Four patients have also been studied before and after sterile acute injury of the myocardium (septal alcoholization). One hundred thirty-eight healthy donors were studied in parallel. Neutrophils with normal MPO content were 96% in controls, >92% in patients undergoing septal alcoholization, 91% in CSA patients, but only 35 and 30% in unstable angina and AMI (STEMI and NSTEMI) patients, compared to 80%, 75% and 2% of patients with giant cell arteritis, acute bone fracture and severe sepsis. In addition, in 32/33 STEMI and 9/21 NSTEMI patients respectively, 20% and 12% of neutrophils had complete MPO depletion during the first 4 hours after the onset of symptoms, a feature not observed in any other group of patients. MPO depletion was associated with platelet activation, indicated by P-selectin expression, activation and transactivation of leukocyte β2-integrins and formation of platelet neutrophil and -monocyte aggregates. The injection of activated platelets in mice produced transient, P-selectin dependent, complete MPO depletion in about 50% of neutrophils. CONCLUSIONS: ACS are characterized by intense neutrophil activation, like other systemic inflammatory syndromes. In the very early phase of acute myocardial infarction only a subpopulation of neutrophils is massively activated, possibly via platelet-P selectin interactions. This paroxysmal activation could contribute to occlusive thrombosis

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ABSTRACT. Objective. The aim of our study was to evaluate the safety and the efficacy of tocilizumab (TCZ) for refractory Takayasu arteritis (TA). Methods. We retrospectively assessed the outcome of blocking interleukin (IL)-6 with TCZ in 7 consecutive patients with refractory TA using a combination of clinical and imaging assessment. Results. During a median followup visit at 14 months, 4 patients taking TCZ [including 2 nonresponders to tumor necrosis factor (TNF) inhibitors] achieved clinical response, suggesting a nonredundant role for IL-6 in TA. Inflammatory markers normalized in all patients treated with TCZ. However, vascular progression occurred in 4 patients, suggesting the involvement of other inflammatory pathways and confirming the limitations of erythrocyte sedimentation rate and C-reactive protein for disease activity assessment while taking TCZ. Three patients experienced adverse events and 2 suspended TCZ. Conclusion. TCZ may be effective in a subset of patients with refractory TA, even in cases of unresponsiveness to TNF inhibitors. Inflammatory markers are not valid markers of TA activity on TCZ. Further studies are needed to confirm these preliminary observations. (J Rheumatol Firs

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ABSTRACT. Objective. The aim of our study was to evaluate the safety and the efficacy of tocilizumab (TCZ) for refractory Takayasu arteritis (TA). Methods. We retrospectively assessed the outcome of blocking interleukin (IL)-6 with TCZ in 7 consecutive patients with refractory TA using a combination of clinical and imaging assessment. Results. During a median followup visit at 14 months, 4 patients taking TCZ [including 2 nonresponders to tumor necrosis factor (TNF) inhibitors] achieved clinical response, suggesting a nonredundant role for IL-6 in TA. Inflammatory markers normalized in all patients treated with TCZ. However, vascular progression occurred in 4 patients, suggesting the involvement of other inflammatory pathways and confirming the limitations of erythrocyte sedimentation rate and C-reactive protein for disease activity assessment while taking TCZ. Three patients experienced adverse events and 2 suspended TCZ. Conclusion. TCZ may be effective in a subset of patients with refractory TA, even in cases of unresponsiveness to TNF inhibitors. Inflammatory markers are not valid markers of TA activity on TCZ. Further studies are needed to confirm these preliminary observations. (First Release Nov