Steroid-Induced Leukocytosis or "Left Shift" - Time Effects

3/11/02 (Difrancesco)

Question: Can there be a "left shift" resulting from steroid therapy, and how long-lasting are those effects?

<2>

Unique Identifier:10096263

Authors: Chakraborty A. Blum RA. Cutler DL. Jusko WJ.

Institution: Department of Pharmaceutics, School of Pharmacy, State University of New York at Buffalo, 14260, USA.

Title: Pharmacoimmunodynamic interactions of interleukin-10 and prednisone in healthy volunteers.

Source: Clinical Pharmacology & Therapeutics. 65(3):304-18, 1999 Mar.

Abstract: OBJECTIVE: The pharmacoimmunodynamic interactions of recombinant human interleukin-10 and prednisolone were examined in 12 normal male volunteers. METHODS: Single doses of interleukin-10 (8 microg/kg subcutaneous injection), interleukin-10 with prednisone (15 mg by mouth), placebo with prednisone, or placebo were administered. Drug concentrations yielded pharmacokinetic parameters. Response measurements included whole blood lipopolysaccharide-stimulated cytokine (tumor necrosis factor-alpha, interleukin-1beta) production, phytohemagglutinin-stimulated whole blood lymphocyte proliferation, and differential white blood cell counts (including monocytes, lymphocytes, and neutrophils). Extended indirect-response models were used to deal with diverse drug interactions in assessing single and joint effects of interleukin-10 and prednisolone. RESULTS: No pharmacokinetic alterations in interleukin-10 or prednisolone were found. Dosing with interleukin-10 produced strong inhibition of ex vivo cytokine production for the 24-hour postdosing period, whereas prednisolone, the active form of prednisone, was partly inhibitory for only 3 hours. Prednisolone significantly inhibited (P < .05) ex vivo lymphocyte proliferation for 6 hours, whereas interleukin-10 failed to alter this measure. Their joint effects on these responses were inhibitory consonant with the stronger agent. Marked changes in various leukocyte kinetics occurred. The steroid caused monocytopenia, lymphocytopenia, and neutrophilia, with IC50 or SC50 values of 10 to 20 ng/mL. Interleukin-10 elevated monocytes and neutrophils and lowered lymphocyte counts, with IC50 or SC50 values of 0.7 to 1.3 ng/mL. Dynamic modeling showed loss of prednisolone effects on monocytes and additive steroid/interleukin-10 effects on lymphocytes and neutrophils, with neutrophils exhibiting greater changes in net response. CONCLUSION: Interleukin-10 and prednisolone interacted favorably for the measured pharmacoimmunodynamic indices with no kinetic alterations but net responses that were similar to or greater than effects produced by the more strongly acting agent. CAS Registry/EC Number 0 (Anti-Inflammatory Agents, Steroidal). 0 (Cytokines). 0 (Recombinant Proteins). 130068-27-8 (Interleukin-10). 53-03-2 (Prednisone).

<

<4>

Unique Identifier:1702407

Authors: Brohee D. Vanhaeverbeek M. Kennes B. Neve P.

Institution: Department of Internal Medicine, (Universite Libre de Bruxelles), CHU Andre Vesale, Montigny-le-Tilleul, Belgium.

Title: Leukocyte and lymphocyte subsets after a short pharmacological stress by intravenous epinephrine and hydrocortisone in healthy humans.

Source: International Journal of Neuroscience. 53(2-4):53-62, 1990 Aug.

Abstract: Nine healthy volunteers received epinephrine and hydrocortisone intravenously in order to assess the typical acute response to a brief stress, of leukocyte and lymphocyte subsets, acute phase reactants and lymphocyte reactivity to T and B mitogens. At 10 min., all leukocyte subsets were increased, especially mononuclear cells. At 1 hour, moderate lymphopenia and monocytopenia occurred. At 6 hours, neutrophilia and eosinopenia were observed. During the lymphocytic early wave, all the lymphocyte subset counts increased, particularly T-suppressive/cytotoxic and natural killer cells. As a consequence, the percentage of T cells decreased and the CD4/CD8 ratio fell. No changes in acute phase reactants occurred over the 24 hours of the study. All leukocyte and lymphocyte subsets were normalized and mitogen reactivity was unchanged 24 hours after the stress. These typical shifts in leukocyte subsets could probe the adrenocortical and medullary response to an environmental stressor. CAS Registry/EC Number 0 (Acute-Phase Proteins). 0 (Mitogens). 50-23-7 (Hydrocortisone). 51-43-4 (Epinephrine).

<5>

Unique Identifier:6263290

Authors: Perez HD. Kimberley RP. Kaplan HB. Edelson H. Inman RD. Goldstein IM.

Title: Effect of high-dose methylprednisolone infusion on polymorphonuclear leukocyte function in patients with systemic lupus erythematosus.

Source: Arthritis & Rheumatism. 24(5):641-7, 1981 May.

Abstract: We have studied the effect of high-dose (1 gm) methylprednisolone infusion on polymorphonuclear leukocyte (PMN) function in 11 patients with active systemic lupus erythematosus (SLE). The only alteration of polymorphonuclear leukocyte function produced consistently by methylprednisolone was decreased adherence to plastic surfaces when tested 2 hours after infusion. This steroid-induced abnormality, however, was transient. Cells obtained from patients 24 hours after a single dose of drug exhibited normal adhesiveness. These results indicate that single, large doses of methylprednisolone do not produce long-lasting abnormalities of PMN function in patients with lupus. CAS Registry/EC Number 11062-77-4 (Superoxides). 83-43-2 (Methylprednisolone). EC 3-2-1-31 (Glucuronidase).