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Lupus relapse after prostaglandin E1 administration: activation of a cytokine cascade?
  1. M de la Torre1,
  2. R Alcázar1,
  3. D Sánchez de la Nieta1,
  4. J Nieto1,
  5. I Ferreras1,
  6. J M Urra2
  1. 1Nephrology and Services, Complejo Hospitalario Ciudad Real, Spain
  2. 2Immunology Service, Complejo Hospitalario Ciudad Real, Spain
  1. Correspondence to:
    Dr M de la Torre, Servicio de Nefrología, Complejo Hospitalario de Ciudad Real, 13002 Ciudad Real, Spain;
    mtorref{at}nexo.es

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A variety of abnormalities in cytokine production occur in human and murine lupus, but their specific role in lupus pathogenesis is unknown.1 Recent in vitro studies emphasise the role of prostaglandins in the cytokine induction and modulation of the humoral immune response.2,3 We present a patient with systemic lupus erythematosus (SLE) who had a relapse after prostaglandin E1 (PGE1) administration, which to our knowledge has not been previously reported.

A 25 year old woman was admitted to hospital to receive treatment with IV PGE1 owing to severe Raynaud's phenomenon. Fifteen years previously SLE had been diagnosed according to American Rheumatism Association (ARA) criteria, with renal biopsy proven diffuse proliferative lupus glomerulonephritis (WHO class IV). A physical examination showed only painful, violaceous, and atrophic finger pads with no signs of systemic inflammatory disease. The chest x ray films were normal and laboratory investigations showed antinuclear antibodies (ANA; titre 1/160) and hypocomplementaemia (C3 0.6 g/l, C4 0.1 g/l), with normal liver, renal, and haematological parameters. Treatment with 40 mg/12 h IV PGE1 was started. On the sixth day of treatment the patient began to have chest pain, fever, dyspnoea, and pericardial friction rub. The laboratory showed anaemia, modest thrombocytopenia, and ANA 1/320, with no changes in the rest of the biochemical serum parameters. Echocardiography and chest x ray examination showed moderate pericardial and bilateral pleural effusions. PGE1 was withdrawn and oral prednisone, 60 mg/day, was started with prompt improvement in the symptoms.

We investigated the possibility that PGE1 mediated cytokine production might be the cause of the relapse of SLE in this patient. Intracellular expression of cytokines in the patient's T lymphocytes after specific PGE1 stimuli (10 ng/ml) was determined by flow cytometry using anticytokine conjugates in combination with surface anti-CD3 (Pharmingen, San Diego, CA), as previously described.4 The test performed eight months after the PGE1 treatment showed a dramatic rise in interleukin 4 (IL4) production (table 1).

It has been suggested that cytokines have an important role in the immune dysregulation seen in lupus prone mice and in patients with SLE. Increasing evidence supports a role for T helper cell type 2 (Th2) cytokines, such as IL4, in promoting and perpetuating B cell hyperactivity and autoantibody formation.1,5,6 A change in the proportion of Th2 cytokines might be associated with the polyclonal B cell activation seen in SLE.7–9 Restoration of Th1 and Th2 cytokines to levels similar to those seen in healthy mice results in amelioration of the clinical manifestations of an already established experimental SLE.10

On the other hand, in some studies it has been suggested that PGE1 alters the Th1/Th2 balance of T cells to a dominant Th2 response.11 We suggest that the rise in IL4 production induced by the PGE1, as shown in vitro in this patient, may be a marker of dysregulation of the Th1/Th2 profile and might have been the cause of her lupus relapse.

Table 1

Intracellular cytokine production after PGE1 stimulation in the patient and in an asymptomatic lupus patient who served as a control. Results are shown as the percentage of T lymphocytes with cytokine synthesis

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