Anti-inflammatory and Immunomodulatory Effects of Antibiotics and Their Use in Dermatology.

Antibiotics (antibacterial, antiviral, and antiparasitic) are class of drugs which result in either killing or inhibiting growth and multiplication of infectious organisms. Antibiotics are commonly prescribed by all specialties for treatment of infections. However, antibiotics have hitherto immunomodulatory and anti-inflammatory properties and can be exploited for various noninfectious dermatoses. Dermatologists routinely prescribe antibiotics in treatment of various noninfectious disorders. This study will review anti-inflammatory and immunomodulatory effects of antibiotics and their use in dermatology.

What was known?

Antibiotics are mainly considered as anti-bacterial agents used for infectious conditions

In dermatology antibiotics are being used for various infectious conditions.

Introduction

Antibiotics are chemicals derived from microorganisms that have the capacity, in dilute solutions, to kill other microorganisms (bacteria, virus, fungi, and parasite) or inhibit their growth. In this study, antibiotics refer to collective term for antibacterial, antiviral, and antiparasitic agents. In routine clinical practice, antibiotics are chiefly used to eliminate various pathogens (bacteria, viruses, and parasites). Many antibiotics were later found to have anti-inflammatory properties apart from their antimicrobial action. We have discussed anti-inflammatory and anti-immunomodulatory effects of various antibacterial and antiparasitic drugs. Antiviral and antifungal drugs are seldom used for their anti-inflammatory properties.

Antibacterial Agents

Clindamycin

Clindamycin is a synthetic derivative of lincomycin and isolated from the Streptomyces species. The drug has broad-spectrum antibacterial action by binding irreversibly to 50S subunit of bacterial ribosome and thereby inhibiting bacterial protein synthesis. In dermatology, clindamycin is being used for several indications for its both antibacterial and anti-inflammatory properties [Table 1].

Table 1

Indications of clindamycin as an anti-inflammatory agent

Clofazimine

Clofazimine is a iminophenazine dye known for its antimycobacterial properties. Its absorption is increased with food. It is highly lipophilic and concentrates in lipid-rich tissues. Because of slow elimination, the drug has long half-life of approximately 70 days. Metabolism of the drug occurs in liver and elimination occurs through sebum, sputum, tears, sweat, and urine. However, it also possesses good anti-inflammatory actions and is used in many dermatologic diseases for the same [Table 2].

Table 2

Indications of clofazimine as an anti-inflammatory agent

Dapsone

Dapsone (4,4’-diaminodiphenylsulfone) is an aniline derivative belonging to the group of synthetic sulfones. Dapsone is absorbed rapidly and nearly completely from the gastrointestinal tract. Peak plasma concentration is reached within 2–8 h after administration. The mean half-life of elimination is about 20–30 h. It is metabolized in liver by two distinct routes, N-acetylation and N-hydroxylation. It has dual functions of both antimicrobial/antiprotozoal effects and anti-inflammatory features similar to nonsteroidal anti-inflammatory drugs. Dapsone has been used as a treatment option in various dermatological conditions because of its anti-inflammatory effects [Table 3].

Table 3

Indications of dapsone for its anti-inflammatory and immunomodulatory properties

Macrolides

Macrolides contain a macrocyclic lactone ring structure. These are of actinomycetes or semisynthetic derivatives of same bacteria. They are bacteriostatic antibacterial agents which bind irreversibly to the large (50S) ribosomal subunit of bacteria, thereby inhibiting RNA-dependent protein synthesis. However, there have been many dermatological uses of macrolides for their immunomodulatory action. Azithromycin (A), roxithromycin (R), erythromycin (E), and clarithromycin (C) are commonly used in dermatology practice for their immunomodulatory and anti-inflammatory potential [Table 4].

Table 4

Indications of macrolides in dermatological diseases for their its anti-inflammatory and immunomodulatory properties

Metronidazole

Metronidazole is a synthetic nitroimidazole antibacterial drug. It acts by DNA disruption and nucleic acid synthesis inhibition. It acts against anaerobic bacteria and protozoa. However, it has many actions other than its antibacterial action for which it is being used in different dermatological diseases [Table 5].

Table 5

Indications of metronidazole for its anti-inflammatory properties

Rifampicin

Rifampicin (R) is a semisynthetic derivative of rifamycin B, an antimicrobial agent produced by Streptomyces mediterranei. It is a broad-spectrum antimicrobial and inhibits the growth of most Gram-positive bacteria, as well as many Gram-negative microorganisms. However, it has other properties besides antimicrobial action for which it has been used in various dermatological conditions [Table 6].

Table 6

Indications of rifampicin for its anti-inflammatory and immunomodulatory properties

Tetracyclines

The tetracyclines are broad-spectrum antibiotics and comprise four main drugs (tetracycline [T], doxycycline [D], minocycline [M], and lymecycline [L]). Tetracycline group of antibacterial agents are indicated in a wide range of infections including Treponema pallidum (syphilis), Borrelia burgdorferi, Borrelia afzelii, Borrelia garinii (Lyme disease), Coxiella burnetii (Q fever), Rickettsia rickettsii (Rocky Mountain spotted fever), and Yersinia pestis (Plague). Their antibiotic effect is primarily exerted by binding to the 30S subunit of bacterial ribosomes, thereby halting protein synthesis. However, many tetracyclines have in addition anti-inflammatory properties. [Table 7] discusses the role of tetracyclines chiefly for their anti-inflammatory properties.

Table 7

Indications of tetracyclines in dermatology for their its anti-inflammatory properties

Antimalarials

The parent molecule for the antimalarials is quinine. Among antimalarials, chloroquine (CQ) and hydroxychloroquine (HCQ) are used in various dermatological disorders. Both CQ and HCQ are alkylated 4-aminoquinolines. HCQ is a derivative of CQ and is nearly completely absorbed within 2–4 h of an oral dose and metabolized in liver by dealkylation. The drugs accumulate in thrombocytes, granulocytes, and erythrocytes; hence, their concentration in whole blood is 3–10 times higher than that of plasma. CQ has high affinity for melanin and gets accumulated in the eyes and the skin where the concentration is 100–200 times higher than that of plasma; in the epidermis, it is 3–7 times higher than that of the dermis. The maximum daily dosage is 3.5–4 mg/kg of body weight for CQ and 6–6.5 mg/kg body weight for HCQ. Various indications for antimalarials drug are shown in [Table 8].

Table 8

Indications of antimalarials in dermatology

Levamisole

Levamisole is an anthelmintic agent with a wide range of immunomodulatory actions. It belongs to the class of imidazothiazole derivatives. It is water-soluble and gets rapidly absorbed from the gastrointestinal tract with peak blood levels achieved after 1.5–4 h. Metabolism of the drugs occurs mainly in liver and the plasma half-life is 16 h. Due to immunomodulatory properties, it has been widely used in various dermatological disorders. Usual dose of the drug is 150 mg/day for 2–4 days each week [Table 9].

Table 9

Indications of levamisole in dermatology

Side effects

All the above-discussed drugs have variety of side effects in the therapeutic dose range. The treating skin physician must be aware of commonly encountered side effects which can enable him or her to rationalize the treatment protocol and manage the side effects with due care [Table 10].

Table 10

Commonly encountered side effects of various antibiotics

Conclusions

The study aims to highlight the role of various antibiotic drugs in the management of noninfectious diseases of skin and its appendages. In future, many more cutaneous diseases will be treated and managed with various antibiotics tapping their anti-inflammatory properties. We would like to highlight that in future, these antibiotics will be used albeit in continuous low-dose in various noninfectious dermatoses, thereby minimizing the incidence of side effects.165

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

What is new?

Antibiotics refer to collective term for antibacterial, antiviral, and antiparasitic agents

Antibiotics have multifaceted actions besides killing the infectious organisms

Anti-inflammatory and immunomodulatory effects of antibiotics make them eligible to be used in various non-infectious conditions in dermatology

Anti-parasitic drugs are also used in dermatology for their anti-inflammatory and immunomodulatory properties.