Lymphocyte markers and natural killer cell activity in fibromyalgia syndrome: effects of low-dose, sublingual use of human interferon-alpha.

A clinical study was designed to utilize flow cytometric immunophenotyping and chromium release from cultured tumor target cells to characterize peripheral blood mononuclear leukocyte (PBML) subpopulations and natural killer activity in healthy normal controls (n = 18) and in patients with fibromyalgia syndrome (FMS) at baseline (n = 124) and again after 6 weeks of treatment with low-doses of orally administered human interferon-alpha (IFN-alpha). Volunteer subjects discontinued all analgesic and sedative hypnotic medications for 2 weeks prior to the baseline phlebotomy. Laboratory measures included a complete blood count; a phenotypic analysis of PBML by flow cytometry; and in vitro natural killer (NK) cell activity. After baseline blood sample collection, the FMS patients were randomized to one of four parallel treatment groups (n = 28/group) to receive sublingual IFN-alpha (15 IU, 50 IU, 150 IU), or placebo every morning for 6 weeks. The tests were repeated at week 6 to evaluate treatment effects. At baseline, FMS patients exhibited fewer lymphocytes and more CD25+ T lymphocytes than did normal controls. By week 6, the main significant and consistent change was a decrease in the HLA-DR+ CD4+ subpopulation in the 15 IU and 150 IU treatment groups. These data do not support an immunologically dysfunctional PBML phenotype among patients with FMS as has been observed in the chronic fatigue syndrome.

Elevated cerebrospinal fluid levels of substance P in patients with the fibromyalgia syndrome.

OBJECTIVE: To measure, and seek clinical correlates with, levels of substance P (SP) in the cerebrospinal fluid (CSF) of fibromyalgia syndrome (FMS) patients. METHODS: CSF from 32 FMS patients and 30 normal control subjects was tested for SP by radioimmunoassay. Clinical measures included tender point examination and standardized questionnaires. RESULTS: CSF SP levels were 3-fold higher in FMS patients than in normal controls (P < 0.001), but they correlated only weakly with tenderness found on examination. CONCLUSION: SP is significantly elevated in FMS CSF, but other abnormalities must exist in FMS to more fully explain the symptoms.

Platelet 3H-imipramine uptake receptor density and serum serotonin levels in patients with fibromyalgia/fibrositis syndrome.

The density of serotonin reuptake receptors on peripheral platelets from 22 patients with primary fibromyalgia syndrome (FS) and the serum serotonin concentrations in 9 patients with FS were compared with those of matched healthy controls. The mean serum serotonin concentration was lower (p = 0.01) in FS than in controls, while the binding of 3H-imipramine was higher (p = 0.035) and normalized with treatment using a combination of ibuprofen and alprazolam. Improvement in selected clinical measures of FS disease activity during treatment correlated with the change in platelet 3H-imipramine binding. These findings support the proposed hypothesis of aberrant pain perception in FS resulting from a deficiency of serotonin.

Serum amino acids in fibrositis/fibromyalgia syndrome.

Free plasma tryptophan levels in patients with fibrositis syndrome were measured by Moldofsky and Warsh with the view that the pathogenesis of fibrositis syndrome might involve a functional deficiency of serotonin. The hypothesis was supported by the finding of an inverse relationship between tryptophan concentration and the severity of musculoskeletal pain. Our study examined the total serum amino acid pool in fibrositis syndrome. Twenty patients with primary fibrositis syndrome and matched normal controls were evaluated clinically. After denaturation of macromolecules, serum amino acids were quantitated by automated analysis. Patients with fibrositis syndrome exhibited significantly lower levels of total serum tryptophan (p = 0.002), as well as 6 other amino acids: alanine (p less than 0.0005), histidine (p = 0.001), lysine (p = 0.02), proline (p = 0.039), serine (p = 0.028), and threonine (p = 0.013). These findings support the serotonin deficiency hypothesis for fibrositis syndrome pathogenesis but also imply a more generalized defect in amino acid homeostasis among affected individuals.

Is there a metabolic basis for the fibrositis syndrome?

Patients with the fibrositis syndrome experience moderately severe musculoskeletal discomfort, mood changes associated with nonrestorative sleep, and tenderness to palpation at specific body sites. There is no characteristic abnormal laboratory finding in these patients to help identify the population. A report by Moldofsky and Warsh (Pain 1978; 5: 65-71) of low serum levels of free tryptophan in patients with severe fibrositis syndrome is intriguing but remains unexplained. Those data plus the observation by Hudson et al (Am J Psychiatry 1985; 142: 441-446; Biol Psychiatry 1984; 19: 1489-1493) that patients with fibrositis syndrome exhibit an increased prevalence of anxiety and depression suggest a number of possible avenues for further study. They include potential alterations in the homeostasis of catecholamines, corticosteroids, serotonin, aromatic amino acids, platelet membrane receptor levels, and the activity of platelet membrane monoamine oxidase. Among these possibilities, evidence is now available that suggests an increased production of catecholamines in fibrositis syndrome.