The character of cytokine response in AIDS patients may be directly related to the stimulus employed in test systems. There is no evidence for Th1/Th2 dysregulation. Cytokine elevations in AIDS patients generally are reflective of chronic infection (the virus). Lymphocytes from AIDS patients do not respond as well to stimulation as do those from normal healthy volunteers. The stimulated lymphocyte response in AIDS patients suggests there is underlying low-grade host versus virus reaction in these patients (exaggerated responses of IL-3, IL-4, IL-8, TGF-B).

The efficacy of Human 6 IFN (HLIFN) given in a pulse fashion was determined in a phase II study. Ninety-one cancer patients were evaluated (9 myeloma, 12 breast, 14 prostate, 9 melanoma, 4 renal, 6 astrocytoma, 7 ovarian, 9 large bowel, 7 gastric, 14 head and neck). They all had advanced progressive cancer that was resistant to chemotherapy and/or radiotherapy. Patients were treated by intramuscular injection of 6 X 10(2) I.U./m2 for three consecutive days every four weeks. 84 patients were evaluable. Complete clinical response was obtained in 23 patients (4 myeloma, 2 breast, 5 prostate, 1 melanoma, 1 renal, 2 astrocytoma, 2 ovarian, 2 large bowel, 1 gastric, 3 head and neck). Partial responses were observed in 35 patients (3 myeloma, 7 breast, 6 prostate, 4 melanoma, 1 renal, 2 astrocytoma, 3 ovarian, 4 head and neck). Objective responses were related (P less than 0.01) to serum IFN level, with complete and partial responses (P less than 0.01) more commonly seen in those patients whose serum IFN levels at two hours were in the range of 1000 to 1650 I.U./ml. Side effects resulting from pulse IFN were acceptable for this group of patients and consisted of fever, transient chills, malaise and asthenia, and transient thrombocytopenia and leukocytopenia. The extent of fever was directly related (P less than 0.01) to response, and was most elevated in patients who achieved objective responses. IFN administered in a pulse fashion appears to be more effective than daily IFN and merits further evaluation.

Interferons (IFN) are biological molecules with antiviral, antiproliferative, and immunomodulatory actions. Plasmapheresis (PP) combined with IFN therapy in 24 multiple sclerosis (MS) patients was associated with a rapid increase in detectable IFN levels. We describe the presence of a detectable factor in the serum of MS patients which decreases the efficacy of IFN therapy in these patients. We call this factor "interferon inhibitor factor" (IIF). Standard IFN assay indicates inhibition of WISH cell protection by IFN owing to the presence of IIF in patient's serum. Similar results were also obtained with human fibroblast and human leukocyte IFNs. The best results were obtained with an IFN mixture; results with 1:20 diluted patient's sera showed elevation of 120% greater than 1:10 dilution. With 1:40 dilution, an elevation of 1,041% was noticed. The IIF from patient sera collected during PP was purified and characterized. Native gel electrophoresis of IIF indicates a single protein band; further analysis on SDS gels indicates two bands at the 200 and 21-kD range. ELISA failed to reveal the presence of any anti-IFN antibodies. This study demonstrates the presence of IIF in MS patients' sera which are removed from the circulation by PP. Removal of IIF from circulation was associated with increased IFN levels and clinical improvement as measured by Kurtzke's disability status scale (KDSS).

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The rationale for the use of interferon (IFN) in the treatment of multiple sclerosis (MS) is based on its recognized antiviral and immunomodulating actions. The pathogenesis of MS is believed to be due to an immunologic response in a genetically predisposed individual, localized within the central nervous system white matter, and triggered by exposure to an environmental agent such as a virus. Based on our personal experience we find that the efficacy of IFN therapy is hampered in MS patients by the presence of an interferon inhibitor factor (IIF) in the patients' sera which we have isolated and characterized. When plasmapheresis (PP) was done on 24 MS patients with intermittent 3-day administration of IFN-alpha and human leukocyte IFN, marked increase of IFN in 18 patients and modest increase in three patients correlated with clinical improvement. Three clinical nonresponders showed no increase in IFN levels following therapy. The ability to remove IIF and lymphokine inhibitor factor (LIF) by PP may explain the successful treatment of our patients. We describe the evaluation of helper T cells, suppressor T cells, HLADR antigen, natural killer cells, and monocyte/macrophage cell populations by flow cytometry before and after PP. A significant increase in these immune-competent cells correlated with marked improvement in Kurtzke disability status scale in 13 patients, while eight stabilized. Patients showing progression of the disease either showed decrease or no change in these parameters after therapy. Encouraging results from this pilot study suggest that PP combined with immunomodulatory regimens of IFN may be an effective therapy for MS.

A case of digitoxin-induced thrombocytopenia is reported in a 76-year-old female patient who had been treated with digitoxin over a period of 5 years. This thrombocytopenia was associated with a moderate eosinophilia and clinical signs of severe digitalis intoxication. A search for thromboagglutinins and the culture of lymphocytes provided significantly positive results, establishing consequently the digitoxin’s responsibility. Further evidence is provided by the fact that the discontinuation of digitoxin was followed by a slow return to normal of the platelet count. The administration of digoxin, on the other hand, was perfectly tolerated.

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