Mirthful laughter differentially affects serum pro- and anti-inflammatory cytokine levels depending on the level of disease activity in patients with rheumatoid arthritis

Rheumatology (Oxford). 2006 Feb;45(2):182-6. doi: 10.1093/rheumatology/kei081. Epub 2005 Nov 30.


Objectives: To examine the effect of mirthful laughter in rheumatoid arthritis (RA), we evaluated the levels of serum cytokines before and after patients experienced mirthful laughter.

Methods: Forty-one patients with RA and 23 healthy subjects were enrolled. They listened to 'Rakugo', a traditional Japanese comic story, to induce mirthful laughter. We measured serum IL-6, IL-1beta, TNF-alpha, IL-4 and IL-1 receptor antagonist (IL-1Ra) concentrations before and after patients listened to the story. The RA subjects were divided into two groups. One was designated the 'difficult-to-control RA' group (CRP > or =1.0 mg/dl); The other group was regarded as the 'easily controlled RA' group (CRP <1.0 mg/dl).

Results: The basal levels of serum IL-6 and TNF-alpha in the RA patients were significantly higher than those in the healthy group. After experiencing mirthful laughter, the levels of serum IL-6 decreased significantly in the RA group but not in the healthy subjects. Interestingly, the level of serum TNF-alpha decreased only in the easily controlled RA group. Serum IL-4 concentration in the RA group was significantly higher than that in healthy subjects before the story. After the story, the level of serum IL-4 significantly decreased in the RA group, especially in the difficult-to-control RA group. In contrast, serum IL-1Ra concentration was statistically higher in the RA group than that in healthy subjects before the story, and a further increase was observed after the story, especially in the easily controlled RA group.

Conclusions: Our findings suggest that mirthful laughter affects the levels of serum pro- and anti-inflammatory cytokines differentially, depending on the RA disease activity.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antirheumatic Agents / therapeutic use
  • Arthritis, Rheumatoid / drug therapy
  • Arthritis, Rheumatoid / immunology*
  • C-Reactive Protein / analysis
  • Cytokines / blood*
  • Humans
  • Interleukin-6 / blood
  • Laughter*
  • Middle Aged
  • Tumor Necrosis Factor-alpha / metabolism


  • Antirheumatic Agents
  • Cytokines
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • C-Reactive Protein