Biology of Disease

The second generation of immunosuppressive treatments target T lym-
phocytes rather than B cells. These included the use of antilymphocyte
globulin, an antibody raised against human T lymphocytes. The third gen-
eration of immunosuppressive treatments are much more selective in their
action and target only those T cells which have been activated by an antigen.
Cyclosporin A, a cyclic peptide (Figure 6.17) derived from the soil fungus
Tolypocladium inflatum gams, is most commonly used. The peptide shows
considerable immunosuppressive action, without the bone marrow toxic-
ity demonstrated by other drugs. Tacrolimus, a macrolide antibiotic (Figure
6.18) derived from Streptomyces tsukubaensis, is similar to cyclosporin A in
action. It is more powerful than cyclosporin A but also has more side effects.
Mycophenolate mofetil is an example of a prodrug, which is converted in the
body to mycophenolic acid, another powerful immunosuppressive agent.

Figure 6.17Cyclosporin A.

IMMUNOSUPPRESSION

CZhhVg6]bZY!BVjgZZc9Vlhdc!8]g^hHb^i]:YLddY &*&

N

N

N

N

N

N

N

O O

O O O

O O

O O

O

O

CH 3

CH 3

CH 3

N N

CH 3

CH 3

CH 3

H

H

N N

H

H

CH 3

CH 3

CH 3

CH 3

CH 3

CH 3

CH 3

H 3 C

H 3 C

H 3 C

H 3 C

CH 3

CH 3

H 3 C

H 3 C

H 3 C HO

H 3 C CH 3

HO

HO

H

H

H

H

H

H

H

H H

H

H

H

H

H 3 CO

OCH 3

H 3 C

H 3 C

N

OH

CH 3

CH 3

CH 3

CH 2

OCH 3

O

O

O O

O

O

Figure 6.18Tacrolimus.