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The recovery of acromegaly is not obtained in about 50 percent of cases treated with radiotherapy and/or transsphenoidal surgery. Somatostatin analogs prescribed in such cases are effective but need either several subcutaneous injections a day or continuous infusions with pumps. Long-acting formulations of the new somatostatin analog lanreotide should avoid such drawbacks. Nine acromegalics, not cured by pituitary surgery (associated with radiotherapy in 7) received on IM injection of a long acting formulation of lanreotide twice a month for one year. Basal evaluation included: clinical examination, routine analyses, gall bladder ultrasonography, hormonal investigation of pituitary function including GH and IgF-1 measurements, visual field evaluation and pituitary scanning. A similar evaluation was performed on months 6 and 12 of treatment. The clinical symptoms of acromegaly progressively improved during therapy. Plasma GH levels decreased significantly (P < 0.01) from 24.2 +/- 2.1 to 9.3 +/- 1.2, 6.4 +/- 1.4 and 7.9 +/- 1.1 micrograms/l on months 3, 6 and 12, respectively. Plasma IgF-1 levels were normalized, decreasing from 676 +/- 40 to 331 +/- 30, 350 +/- 36, and 317 +/- 29 ng/ml on months 3, 6 and 12, respectively. Plasma lanreotide levels remained stable throughout the treatment. Side-effects included slight and transient diarrhoea and abdominal cramps which disappeared after 6 months of treatment. No gallstones appeared during treatment. These results show that one injection, twice a month, of a long-acting formulation containing 30 mg lanreotide is able to control the evolutivity of acromegalies not cured by pituitary radiotherapy and/or transsphenoidal surgery. Such formulations are well tolerated and avoid the drawbacks of either several subcutaneous injections a day or continuous infusions of somatostatin analogs.

The pharmacologic modulation of the effect of platelet-activating factor (PAF) on the interleukin-1 (IL-1) activity present in the supernatants from lipopolysaccharide (LPS)-stimulated macrophages was investigated. Rat spleen macrophages were isolated by centrifugation on a Ficoll-Hypaque gradient followed by adherence on plastic petri dishes for 60 min at 37 degrees C under a 5% CO2/95% air atmosphere. The IL-1 content in the cell-free supernatants was assessed using the mouse thymocyte proliferation assay. Preincubation of macrophages for 10 min with 10 fM PAF prior to stimulation with 20 micrograms/ml LPS for 24 h markedly increased the IL-1 activity present in the supernatants from macrophages whereas no direct effect of PAF was noted. Although they had no direct effect, addition of L-651,392 (10 microM), a lipoxygenase inhibitor, or the oxygen-derived free radical scavenger mannitol (10 microM) during the 10-min preincubation period with PAF reversed by 105.0% and 79.9%, respectively, the action of the autacoid on IL-1 activity. Pertussis toxin (PT, 1 microgram/ml) decreased by 30% the LPS-induced IL-1 activity. Association of PT with PAF suppressed the enhancing effect of 10 fM PAF on the IL-1 activity present in the supernatants from LPS-stimulated macrophages. Thus, the enhancing effect of PAF on IL-1 release appears to be due to the production of lipoxygenase metabolites, leading to superoxide production and alterations of cAMP levels.