title: Mirthful laughter differentially affects serum pro- and anti-inflammatory cytokine levels depending on the level of disease activity in patients with rheumatoid arthritis.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Joint Disease and Rheumatism, Nippon Medical School, Tokyo, Japan. matsuzaki@nms.ac.jp
authors.forename: T
authors.initials: T
authors.lastname: Matsuzaki
authors.forename: A
authors.initials: A
authors.lastname: Nakajima
authors.forename: S
authors.initials: S
authors.lastname: Ishigami
authors.forename: M
authors.initials: M
authors.lastname: Tanno
authors.forename: S
authors.initials: S
authors.lastname: Yoshino
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000276:immunology*; D002097:C-Reactive Protein / Q000032:analysis; D016207:Cytokines / Q000097:blood*; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D007845:Laughter; D008875:Middle Aged; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D018501:Antirheumatic Agents; D016207:Cytokines; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein