Interleukin-2 in the treatment of HIV disease

Schwartz, David H.; Merigan, Thomas C.

doi:10.1007/bf02173452

Cited by 16 publications

(3 citation statements)

References 154 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…112 The administration of immunomodulators such as interleukin-2 results in a profound release of these cytokines. 113,114 In a study of HIV-infected patients who were receiving a five-day infusion of interleukin-2, the area under the curve for plasma indinavir was increased by 75 percent. 115 …”

Section: Drug-cytokine Interactionsmentioning

confidence: 99%

Interactions among Drugs for HIV and Opportunistic Infections

2001

View full text Add to dashboard Cite

Section: Drug-cytokine Interactionsmentioning

confidence: 99%

Interactions among Drugs for HIV and Opportunistic Infections

2001

View full text Add to dashboard Cite

“…One focus involves attempts to utilize cytokines for their antiviral properties or to enhance the patient's immune system. Therapy with two cytokines, alpha interferon (IFN-␣) and interleukin-2 (IL-2), is being evaluated in clinical trials since these agents demonstrate both in vitro properties and clinical results which suggest that they may provide benefit to patients infected with HIV (7,8,11,16,18,19).…”

mentioning

confidence: 99%

Effects of cytokines on antiviral pharmacokinetics: an alternative approach to assessment of drug interactions using bioequivalence guidelines

Piscitelli

Amatea

Vogel

et al. 1996

Antimicrob Agents Chemother

View full text Add to dashboard Cite

The effects of cytokines on the pharmacokinetics of nucleoside analogs were evaluated in two separate studies using zidovudine in combination with interleukin-2 and didanosine in combination with alpha interferon. In each study, drug interactions were evaluated by using both a standard method (Student's t test) and bioequivalence testing. Serial blood samples were collected from human immunodeficiency virus-infected patients prior to and during cytokine therapy for determination of nucleoside analog concentrations. Concentrations were fit separately to a two-compartment model by using the iterative two-stage approach to population analysis. No alterations in area under the curve or oral clearance were observed for either drug during combination therapy. In general, there was good agreement between statistical methods for determining if antiviral pharmacokinetic parameters were altered by concomitant cytokine therapy. However, large individual changes in the maximum concentration of zidovudine in serum were detected by bioequivalence testing but no difference was found by Student's t test. For didanosine, significant but clinically irrelevant decreases determined by standard hypothesis testing were seen for both the volume of the central compartment (1.91 to 1.86 liters) and the absorption rate constant (0.79 to 0.73 h-1) in the presence of alpha interferon. No interaction was noted for these parameters by using bioequivalence guidelines. Bioequivalence testing may provide an alternative approach to assessment of drug interactions. Interleukin-2 and alpha interferon do not alter the pharmacokinetics of zidovudine and didanosine, respectively.

show abstract

“…IL-2 has been shown to boost in vitro NK and ADCC responses in HIV-I ' individuals (reviewed in [5,6,12]). The corresponding potential of IL-2 to induce LAK cytolylic responses in seropositive individuals has not been established.…”

Section: Introductionmentioning

confidence: 99%

Changes in natural immunity during the course of HIV-1 infection

Brenner

Gryllis

Gornitsky

et al. 1993

Clinical and Experimental Immunology

View full text Add to dashboard Cite

SUMMARY The role of natural killer (NK) and lymphokine‐activated killer (LAK) cell‐mediated cytotoxiciry in AIDS has yet to be established. The objective of this study was to determine inducible LAK cell responses at different stages of HIV‐1 infection, and specifically to establish the participation of CD8 lymphocytes in these responses. Peripheral blood lymphocytes (PBL) were isolated from healthy seronegative (CDC‐0) subjects and HIV‐1 individuals who were clinically asymptomatic (Centre for Disease Control group 2, CDC‐2) or symptomatic (CDC‐4) with regard to secondary opportunistic infection (OI). LAK cells were generated upon incubation of PBL with IL‐2 and their cytolysis of K562 and U‐937 targets was determined using chromium release assays. The role of CD8+ lymphocytes as progenitors and effectors of these LAK cell responses was determined by immunomagnetic depletion of CD8+ cells from precursor PBL and LAK cells, respectively. LAK cell‐mediated cytotoxicities in HIV‐1‐infected individuals were reduced compared with scronegativc controls without any corresponding changes in the relative proportions of CD56+ (NK) cells among groups. Depletions of CD8+ subsets from either PBL or LAK cells dramatically reduced total LAK cytotoxic responses and LAK activities per unit CD56+ cell in the OI‐CDC‐2 scropositive population. No corresponding changes in LAK activities in seronegative control or HIV+/OI+ CDC‐4 groups were observed. Levels of LAK activity against K562 targets in CDC‐0/HIV and CDC‐4/HIV+ groups correlated with the percentage of CD56+ LAK cells; corresponding LAK activity in the CDC‐2/HIV+ group correlated with the percentage of both CD56+ and CD8+ subsets. These findings suggest that adaptive changes in non‐MHC restricted cytotoxic responses occur in HIV‐1 individuals at early stages post‐HIV infection, before the onset of opportunistic infection.

show abstract

Interleukin-2 in the treatment of HIV disease

Cited by 16 publications

References 154 publications

Interactions among Drugs for HIV and Opportunistic Infections

Interactions among Drugs for HIV and Opportunistic Infections

Effects of cytokines on antiviral pharmacokinetics: an alternative approach to assessment of drug interactions using bioequivalence guidelines

Changes in natural immunity during the course of HIV-1 infection

Contact Info

Product

Resources

About