Cytokine profiles in patients with newly diagnosed multiple myeloma: Survival is associated with IL-6 and IL-17A levels

Cytokine. 2021 Feb:138:155358. doi: 10.1016/j.cyto.2020.155358. Epub 2020 Nov 10.

Abstract

Background: Identifying specific risk factors associated with multiple myeloma (MM) remains a significant issue. Different cytokines take part in the pathogenesis, progression, and prognosis of MM. Therefore, this study aimed to investigate the correlations between serum cytokine levels and clinical characteristics and determine their effects on disease progression and survival of MM patients.

Methods: We retrospectively analyzed the serum levels of 7 cytokines in 105 patients with newly diagnosed MM and in 20 healthy subjects. Interleukin (IL)-2, IL-4, IL-6, IL-10, and IL-17A, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ were quantitatively determined by cytometric bead assay techniques. The concentrations of each cytokine were compared between the MM patients and healthy subjects using the Mann-Whitney U test. The Kaplan-Meier method was used to analyze progression-free survival (PFS) and overall survival (OS).

Results: Serum IL-2, IL-4, IL-6, IL-10, IL-17A, TNF-α, and IFN-γ levels were higher in patients with newly diagnosed MM than in healthy controls. Positively significant correlations were found between IL-6, IL-10, IL-17A, and β2-microglobulin. Significant correlations were also observed between IL-6 and IL-10, and lactate dehydrogenase. The overall response rate of low-IL-6 and IL-17A patients was significantly higher than that of high-IL-10 and IL-17A patients (P < 0.01). Univariate and multivariate analyses revealed that serum IL-6 levels were >3 pg/mL, serum IL-17A levels were >4 pg/mL, and treatment regimens were independent prognostic factors for PFS and OS.

Conclusions: Cytokine deregulation, especially that of IL-6 and IL-17A, may be a powerful predictor of clinical prognosis for MM patients.

Keywords: Cytokine deregulation; Cytokine profiles; IL-17A; IL-6; Multiple myeloma; Survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cytokines / metabolism
  • Disease Progression
  • Female
  • Flow Cytometry
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Interferon-gamma / blood
  • Interleukin-10 / blood
  • Interleukin-17 / blood*
  • Interleukin-2 / blood
  • Interleukin-4 / blood
  • Interleukin-6 / blood*
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Multiple Myeloma / blood*
  • Prognosis
  • Progression-Free Survival
  • Proportional Hazards Models
  • Retrospective Studies
  • Risk Factors
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / blood

Substances

  • Cytokines
  • IL10 protein, human
  • IL17A protein, human
  • IL2 protein, human
  • IL4 protein, human
  • IL6 protein, human
  • Interleukin-17
  • Interleukin-2
  • Interleukin-6
  • TNF protein, human
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interleukin-4
  • Interferon-gamma