Bronchoalveolar lavage (BAL) leukocyte-secreted cytokines are considered to be important mediators of the inflammatory and allergic reactions in the lung. This study examines quantitative changes in the level of tumor necrosis factor-alpha (TNF alpha) and interferon-gamma (IFN gamma) production in BAL cell cultures derived from patients (n = 11) with bronchial asthma. The secretion of TNF alpha and IFN gamma was determined in intact (unstimulated) and phytohemagglutinin/phorbol myristate acetate (PHA + PMA)-stimulated BAL leukocyte cultures and compared with that in control cultures. In all patients studied, the background and PHA + PMA-induced secretion of TNF alpha and IFN gamma was significantly (p < 0.001) higher than that in parallel control cultures. In contrast to BAL cell preparations, the capacity of TNF alpha and IFN gamma secretion by patients' peripheral blood mononuclear cells (PBMC) did not differ from that of control subjects. High spontaneous release of TNF alpha and IFN gamma by patients' BAL leukocytes, but not PBMC, suggest that in the pathophysiology of bronchial asthma, these cytokines may act as local pathogenic agents in the lung.
Background:The involvement of inflammatory components in the pathophysiology of low back pain (LBP) is poorly understood. It has been suggested that spinal manipulative therapy (SMT) may exert anti-inflammatory effects.Purpose:The purpose of this study was to determine the involvement of inflammation-associated chemokines (CC series) in the pathogenesis of nonspecific LBP and to evaluate the effect of SMT on that process.Methods:Patients presenting with nonradicular, nonspecific LBP (minimum pain score 3 on 10-point visual analog scale) were recruited according to stringent inclusion criteria. They were evaluated for appropriateness to treat using a high velocity low amplitude manipulative thrust in the lumbar-lumbosacral region. Blood samples were obtained at baseline and following the administration of a series of 6 high velocity low amplitude manipulative thrusts on alternate days over the period of 2 weeks. The in vitro levels of CC chemokine ligands (CCL2, CCL3, and CCL4) production and plasma levels of an inflammatory biomarker, soluble E-selectin (sE-selectin), were determined at baseline and at the termination of treatments 2 weeks later.Results:Compared with asymptomatic controls baseline production of all chemokines was significantly elevated in acute (P=0.004 to <0.0001), and that of CCL2 and CCL4 in chronic LBP patients (P<0.0001). Furthermore, CCL4 production was significantly higher (P<0.0001) in the acute versus chronic LBP group. sE-selectin levels were significantly higher (P=0.003) in chronic but not in acute LBP patients. Following SMT, patient-reported outcomes showed significant (P<0.0001) improvements in visual analog scale and Oswestry Disability Index scores. This was accompanied by a significant decline in CCL3 production (P<0.0001) in both groups of patients. Change scores for CCL4 production differed significantly (P<0.0001) only for the acute LBP cohort, and no effect on the production of CCL2 or plasma sE-selectin levels was noted in either group.Conclusions:The production of chemotactic cytokines is significantly and protractedly elevated in LBP patients. Changes in chemokine production levels, which might be related to SMT, differ in the acute and chronic LBP patient cohorts.
Background: Increasing evidence supports somato-visceral effects of manual therapies. We have previously demonstrated that a single spinal manipulative treatment (SMT) accompanied by audible release has an inhibitory effect on the production of proinflammatory cytokines in asymptomatic subjects. The purpose of this study is to report on SMT-related changes in the production of the immunoregulatory cytokine interleukin 2 (IL-2) and to investigate whether such changes might differ with respect to the treatment approach related to the presence or absence of an audible release (joint cavitation).
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