Infectious Diseases in Critical Care Medicine

B-cell depletionvia targeting of the anti-CD20 B-cell surface marker is the anticipated
mechanism of action of rituximab. It is in use or under investigation for several disease entities:
lymphoma, multiple sclerosis, RA, systemic lupus erythematosus, thrombocytopenic
thrombotic purpura, and life-threatening vasculitides. Peripheral measurement of CD19þB
cells can provide insight to immune reconstitution. Lymphocytes may show repletion three
weeks after therapy; however, depletion may last as long as one year.
T-Cell activation and migrationare targeted under several therapies with very different
mechanisms of action. Such therapies include abatacept for RA, alefacept, and efalizumab for
psoriasis and psoriatic arthritis, and natalizumab for multiple sclerosis.
Abatacept inhibits the activation of T cells by mimicking the naturally inducible CTLA-4.
Endogenous CTLA-4 and exogenous abatacept both down-regulate T-cell activity through
higher affinity binding to CD80/CD86 on an antigen-presenting cell (APC), which prevents the
co-stimulatory binding of CD28 of lesser affinity on the T cell. This co-stimulatory binding is

Table 1 Biologic Agents

Biologic agent Mechanism of action Half-life Administration

Anakinra(Kineret) IL-1 receptor antagonist 4 to 6 hours Daily subcutaneous
Adalimumab(Humira) TNF reduction via antibody to TNF-a;
prevents its binding to TNF-a
receptor

2 weeks Subcutaneous injection

every 2 wk

Certolizumab pegol
(Cimzia)

A pegylated mAb under investigation

conferring a longer half-life

2 weeks Subcutaneous injection
weekly
Etanercept(Enbrel) Reduction of circulating TNF via
soluble receptor; partial blockade

4 days Subcutaneous injection
twice weekly
Golimumab A mAb with activity targeting
circulating and membrane-bound
TNF pending approval

7–20 days Subcutaneous or
intravenous monthly
injection
Infliximab(Remicade) Antibody inactivates TNF-a; biologic
activity documented at 2 months

9 days Intravenous infusion at
weeks 0, 2, 6, then
every 8 wk
Abatacept(Orencia) Protein mimics natural CTLA-4;
binds CD80 and CD86 on APC
blocking CD28 on T cell and thus
co-stimulation and activation

8–25 days Intravenous infusion at

weeks 0, 2, 4 then,

every 4 wk

Alefacept(Amevive) Inhibits T-lymphocyte activation by
binding to lymphocyte receptor
CD2, blocking interaction with
LFA-3

11–12 days

(for IV)

Intravenous infusion or
intramuscular injection
weekly for 12 wk;
regimen may be
repeated with 12-wk
interval
Efalizumab(Raptiva) Binds to CD11a of LFA-1 on
leukocytes interfering with multiple
aspects of T-cell activation and
migration

5–8 days Subcutaneous injection

weekly

Rituximab(Rituxin) B-cell lysis via chimeric antibody to
CD20

Approximately

17 days

Two intravenous
infusions, 2 wk apart
for RA
Natalizumab(Tysabri) Antibody toa-4 integrin molecules
blocking T-cell migration into
extravascular tissue

7–15 days Intravenous infusion

every 4 wk

Tocilizumab Antibody to IL-6 receptor 10 days Intravenous infusion
every 4 wk
Anti-JAK3 Inhibits activity of tyrosine kinase
required for JAK3 for transcription

Unknown at

this time

Daily oral

Ustekinumab Inhibits activity of IL-12 and IL-23 20–39 days Subcutaneous injection
every 8–12 wk

Abbreviations: APC, antigen-presenting cell; IL, interleukin; JAK3, janus kinase 3; LFA, leukocyte function–
associated antigen; RA, rheumatoid arthritis; TNF, tumor necrosis factor.

Infections Related to Steroids and Biologics in Critical Care 379