Bj. Johnson et al., CLINICAL AND IMMUNE-RESPONSES OF TUBERCULOSIS PATIENTS TREATED WITH LOW-DOSE IL-2 AND MULTIDRUG THERAPY, Cytokines and molecular therapy, 1(3), 1995, pp. 185-196
Citations number
26
Categorie Soggetti
Cell Biology","Medicine, Research & Experimental",Immunology,Hematology,"Biothechnology & Applied Migrobiology
The immune response to infection with M. tuberculosis depends on cytok
ine activation of effector cells. We therefore conducted a pilot study
of recombinant human interleukin-2 (rhuIL-2) as an adjunct to multidr
ug therapy (MDT) to evaluate the safety of this approach and to determ
ine whether IL-2 can enhance the cellular immune response in patients
with pulmonary tuberculosis (TB). Patients included in this study pres
ented with a wide range of extent and duration of infection, and were
grouped into three categories for data analysis: (1) patients with new
ly diagnosed, acute-stage TB who were lust beginning MDT; (2) patients
who had received a minimum of 45 days MDT before the start of the stu
dy and who had responded to treatment; and (3) patients with multidrug
-resistant (MDR) TB who had been on MDT for at least seven months with
out apparent beneficial clinical response. Twenty patients received 30
days of twice-daily intradermal injections of 12.5 pg of IL-2. Patien
ts from all three groups showed improvement of clinical symptoms over
the 30-day period of treatment with IL-2 and MDT. Results of direct sm
ear for acid fast bacilli (AFB) demonstrated conversion to sputum nega
tive following IL-2 and MDT treatment in all newly diagnosed patients
and in 5/7 MDR TB patients. (The size of the skin test response to pur
ified protein derivative (PPD) of tuberculin Increased during the 30-d
ay IL-2 adjunctive therapy in newly diagnosed patients, but decreased
or disappeared in the other two groups of treated patients.) Assays in
vitro for phenotype distribution, natural killer (NK) cell activity,
frequency of cells proliferating in response to exogenous IL-2, and an
tigen-induced blastogenesis demonstrated systemic responses to Intrade
rmally administered rhuIL-2. Levels of interferon gamma (IFN-gamma) in
plasma, peripheral blood mononuclear cell (PBMC) IFN-gamma mRNA and I
FN-gamma mRNA in biopsy of site of skin test response to purified prot
ein derivative (PPD) were highest in those patients with the most acut
e symptoms at the beginning of the study, and decreased during rhuIL-2
and MDT. IL-2 immunotherapy did not modify levels of mRNA expression
for other cytokines. Patients receiving IL-2 did not experience clinic
al deterioration or significant side effects. These results suggest th
at IL-2 administration in combination with conventional MDT is safe an
d may potentiate the antimicrobial cellular immune response to TB.