Who Is Afraid of CRP? Elevated Preoperative CRP Levels Might Attenuate the Increase in Inflammatory Parameters in Response to Lung Cancer Surgery

Abstract

During surgery, ATP from damaged cells induces the release of interleukin-1β, a potent pro-inflammatory cytokine that contributes to the development of postoperative systemic inflammation, sepsis and multi-organ damage. We recently demonstrated that C-reactive protein (CRP) inhibits the ATP-induced release of monocytic interleukin-1β, although high CRP levels are deemed to be a poor prognostic marker. Here, we retrospectively investigated if preoperative CRP levels correlate with postoperative CRP, leukocyte counts and fever in the context of anatomical lung resection and systematic lymph node dissection as first line lung cancer therapy. No correlation was found in the overall results. In men, however, preoperative CRP and leukocyte counts positively correlated on postoperative days one to two, and a negative correlation of CRP and fever was seen in women. These correlations were more pronounced in men taking statins and in statin-naïve women. Accordingly, the inhibitory effect of CRP on the ATP-induced interleukin-1β release was blunted in monocytes from coronary heart disease patients treated with atorvastatin compared to monocytes obtained before medication. Hence, the common notion that elevated CRP levels predict more severe postoperative inflammation should be questioned. We rather hypothesize that in women and statin-naïve patients, high CRP levels attenuate trauma-induced increases in inflammatory markers.

Perioperative statin medication impairs pulmonary outcome after abdomino-thoracic esophagectomy

“…Statins suppress the expression of adhesion molecules and consecutively inhibit the activation and recruitment of inflammatory cells and decrease inflammasome activity as well as production of pro-inflammatory cytokines including Il-1, Il-6, TNF-α, and CRP in vitro as well as in vivo (Koushki et al 2020 ; Meng et al 2020 ). Thereby, some of the anti-inflammatory effects of statins are mainly responsible for plaque stabilization in atherosclerotic diseases (Koushki et al 2020 ), but statins also systemically affect innate immunity and host defense (Koushki et al 2020 ; Meyer et al 2020 ; Meng et al 2020 ; Jesus Oliveira et al 2020 ; Oliveira et al 2020 ). The role of statins in the regulation of inflammasome activation, especially NLRP3 and consecutively the interleukin-1 release, remains controversial; however, statins suppress Toll-like receptor 4 signaling and NF- k B pathway, which are key players in innate immunity (Koushki et al 2020 ; Meyer et al 2020 ).…”

“…Thereby, some of the anti-inflammatory effects of statins are mainly responsible for plaque stabilization in atherosclerotic diseases (Koushki et al 2020 ), but statins also systemically affect innate immunity and host defense (Koushki et al 2020 ; Meyer et al 2020 ; Meng et al 2020 ; Jesus Oliveira et al 2020 ; Oliveira et al 2020 ). The role of statins in the regulation of inflammasome activation, especially NLRP3 and consecutively the interleukin-1 release, remains controversial; however, statins suppress Toll-like receptor 4 signaling and NF- k B pathway, which are key players in innate immunity (Koushki et al 2020 ; Meyer et al 2020 ). In line with these findings, atorvastatin affects peripheral blood mononuclear cells with reduced production of pro-inflammatory cytokines, including TNF- a and interleukin-6 (Oliveira et al 2020 ).…”

“…Statins interfere with the expression of adhesion molecules and recruitment of inflammatory cells as well as decrease inflammasome activity and pro-inflammatory cytokine or acute phase protein production including interleukin (Il)-1, Il-6, tumor necrosis factor (TNF)-α, and C-reactive protein (CRP) (Koushki et al 2020 ). These effects on inflammation are multifaceted and play a key role in plaque stabilization in atherosclerotic patients, but these effects may also play a role in other cases of systemic inflammation or infection (Koushki et al 2020 ; Meyer et al 2020 ; Krivoy et al 2008 ; Meng et al 2020 ; Jesus Oliveira et al 2020 ; Oliveira et al 2020 ). However, the influence of statins on perioperative inflammatory reaction and patient outcome, especially on postoperative pulmonary outcome in esophagectomy patients, has been poorly investigated until now.…”

Efficacy of multi-groove silicone drains in single-port video-assisted thoracoscopic lung cancer surgery and their effect on C-reactive protein: a single-center experience

“…It is commonly believed that CRP is an acute-phase response protein (10). CRP is mainly produced in the liver in response to IL-1β and IL-6 (40). However, there exists some evidence that CRP also has potential anti-inflammatory functions after lung surgery (41).…”

Sepsis: Current Clinical Practices and New Perspectives: Introduction to the Special Issue

“…The activation of the NLRP3 inflammasome is an essential step in the synthesis of mature IL-1β; thus, it plays a key role in innate immunity. We are proud to present a clinical study of the same group, offering the first findings that elevated preoperative CRP-levels might also be anti-inflammatory and could attenuate the postoperative increase in inflammatory markers [ 9 ]. As a further key player for ATP-mediated monocytic IL-1β release, amyloid-β (1-42) peptide seems to be a modulator of the cholinergic inhibition of the NLRP3 inflammasome.…”