Circulating IL-6 as a predictor of radiation pneumonitis

Chen, Yuhchyau; Rubin, Philip; Williams, John T.; Hernady, Eric; Smudzin, T.; Okunieff, Paul

doi:10.1016/s0360-3016(00)01445-0

Cited by 145 publications

(92 citation statements)

References 24 publications

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“…Inflammatory cytokines have been implicated in the development and perpetuation of post-irradiation injury in various tissues, including the lung [27]. Serum levels of cytokines, in particular, interleukin-6 (IL-6) and transforming growth factor-β (TGF-β), are inconclusive in predicting radiation pneumonitis [28][29][30][31][32]. To what extent such changes are a direct result of radiation as opposed to a consequence of up-regulation of other cytokines and chemokines remains to be established [33,34].…”

Section: Discussionmentioning

confidence: 99%

High superoxide dismutase and low glutathione peroxidase activities in red blood cells predict susceptibility of lung cancer patients to radiation pneumonitis

Park

Ramnath

Yang

et al. 2007

Free Radical Biology and Medicine

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Radiation pneumonitis is an unpredictable complication of radiotherapy for lung cancer and a condition which can cause significant morbidity. The ability to identify patients at a high risk of developing pneumonitis is critical, since it will enable the individualization of the treatment plan. Because the cytotoxic effect of radiation is propagated through ROS and ROS-driven oxidative stress, the role of anti-oxidant defense systems in radiation pneumonitis was investigated. Using the pneumonitis-sensitive C3H/HeN mice as a model, we demonstrated that the anti-oxidant response of the lung correlated well with that of RBC. We then proceeded to test whether differences of RBC anti-oxidant response would predict the pneumonitis development in patients. SOD, GPX, CAT activities and glutathione in RBC were measured at baseline and then weekly for 6 weeks of treatment in fifteen eligible patients receiving concurrent chemo-radiotherapy for unresectable stage III NSCLC. Striking differences were found in the anti-oxidant activities of RBC with respect to the pneumonitis development. Those who developed pneumonitis showed higher SOD and lower GPX activities at baseline compared to those who did not (3.7 vs. 6.8 unit/mg for median SOD, 16.5 vs. 10.7 nmol/min/mg for median GPX). The functional imbalance of SOD and GPX was displayed consistently throughout the treatment period. The sensitivity and specificity of pneumonitis prediction were further increased when the GPX/SOD ratio was analyzed (pre-treatment P = 0.0046). Our results provide a strong rationale to monitor SOD and GPX activities of RBC to identify patients who are at risk of developing pneumonitis, and to implement a strategy of increasing the GPX/SOD ratio in order to lower the risk.

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Section: Discussionmentioning

confidence: 99%

High superoxide dismutase and low glutathione peroxidase activities in red blood cells predict susceptibility of lung cancer patients to radiation pneumonitis

Park

Ramnath

Yang

et al. 2007

Free Radical Biology and Medicine

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“…13 Interferon-g is reported to be a central mediator of pneumonitis, and 2 independent reports have demonstrated a significant correlation with serum IL-6 and pneumonitis in patients receiving pulmonary radiation. [14][15][16] Although the pathogenesis of PI3K-and mTOR-inhibitor-related pneumonitis has yet to be elucidated, pleiotropic effects on cytokine production have been demonstrated, consistent with a proinflammatory response. 17,18 Further, bronchoalveolar lavage findings of a predominance of CD8 1 T cells may suggest a T-cell-mediated autoimmune response.…”

Section: Org Frommentioning

confidence: 99%

Phase 2 study of idelalisib and entospletinib: pneumonitis limits combination therapy in relapsed refractory CLL and NHL

Barr

Saylors

Spurgeon

et al. 2016

Blood

126

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and 9 Gilead Sciences Inc., Foster City, CA Key Points• Concomitant PI3Kd and SYK inhibition resulted in treatment-emergent pneumonitis, necessitating early study termination.• Initial trials of novel combinations should use conservative designs that are focused on safety.Although agents targeting B-cell receptor signaling have provided practice-changing results in relapsed chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL), they require prolonged administration and provide incomplete responses. Given synergistic preclinical activity with phosphatidylinositol 3-kinase d and spleen tyrosine kinase inhibition, this phase 2 study evaluated the safety and efficacy of the combination of idelalisib and entospletinib. Eligible patients with relapsed or refractory CLL or NHL underwent intrapatient dose escalation with each agent. With a median treatment exposure of 10 weeks, 60% and 36% of patients with CLL or follicular lymphoma, respectively, achieved objective responses. However, the study was terminated early because of treatmentemergent pneumonitis in 18% of patients (severe in 11 of 12 cases). Although most patients recovered with supportive measures and systemic steroids, 2 fatalities occurred and were attributed to treatment-emergent pneumonitis. Increases of interferon-g and interleukins 6, 7, and 8 occurred over time in patients who developed pneumonitis. Future studies of novel combinations should employ conservative designs that incorporate pharmacodynamics/biomarker monitoring. These investigations should also prospectively evaluate plasma cytokine/chemokine levels in an attempt to validate biomarkers predictive of response and toxicity.

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“…In einer prospektiven klinischen Studie von Chen et al wurden die IL-6-und TNF-α-Konzentrationen im Blutplasma bei Patienten mit über-wiegend nichtkleinzelligem Bronchialkarzinom vor, während und nach der Bestrahlungsbehandlung bestimmt und mit dem Auftreten einer klinisch apparenten Pneumonitis korreliert [12]. Hohe prätherapeutische IL-6-Plasmaspiegel waren entsprechend dieser Studie mit einem signifikant erhöhten Risiko einer radiogenen Pneumonitis assoziiert.…”

Section: Klinische Bedeutung Von Zytokinblutspiegeln Für Die Ermittluunclassified

Die Bedeutung von Zytokinen für die radiogene Lungenreaktion

2004

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The major pro-inflammatory cytokines in the radiation response of the lung include tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1), and interleukin-6 (IL-6). Transforming growth factor-beta (TGF-beta) appears to be of particular importance in the development of lung fibrosis. First approaches with radioprotective agents and gene therapy to modify radiation-induced cytokine expression have been investigated for prevention of late effects of irradiation lung damage in animal experiments. Preliminary data of clinical studies suggest that elevated plasma TGF-beta-levels during radiotherapy may predict the development of symptomatic radiation pneumonitis. The biological impacts of endogenous radiation-induced cytokine production by tumor cells in respect of tumor behavior, potential damage to normal tissue, and clinical status of the host still need to be determined more precisely.

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Circulating IL-6 as a predictor of radiation pneumonitis

Cited by 145 publications

References 24 publications

High superoxide dismutase and low glutathione peroxidase activities in red blood cells predict susceptibility of lung cancer patients to radiation pneumonitis

High superoxide dismutase and low glutathione peroxidase activities in red blood cells predict susceptibility of lung cancer patients to radiation pneumonitis

Phase 2 study of idelalisib and entospletinib: pneumonitis limits combination therapy in relapsed refractory CLL and NHL

Die Bedeutung von Zytokinen für die radiogene Lungenreaktion

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